Pesticidal compositions and processes related thereto

ABSTRACT

This document discloses molecules having the following formula (“Formula One”): 
                         
and processes related thereto.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. provisional application Ser.No. 61/409,702 that was filed on 3 Nov. 2010 the entire contents of thisU.S. provisional application is hereby incorporated by reference.

FIELD OF THE DISCLOSURE

This disclosure is related to the field of processes to producemolecules that are useful as pesticides (e.g., acaricides, insecticides,molluscicides, and nematicides), such molecules, and processes of usingsuch molecules to control pests.

BACKGROUND

Pests cause millions of human deaths around the world each year.Furthermore, there are more than ten thousand species of pests thatcause losses in agriculture. The world-wide agricultural losses amountto billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. Theworld-wide termite damage losses amount to billions of U.S. dollars eachyear.

Stored food pests eat and adulterate stored food. The world-wide storedfood losses amount to billions of U.S. dollars each year, but moreimportantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developingresistance to pesticides in current use. Hundreds of pest species areresistant to one or more pesticides. The development of resistance tosome of the older pesticides, such as DDT, the carbamates, and theorganophosphates, is well known. But resistance has even developed tosome of the newer pesticides.

Therefore, for many reasons, including the above reasons, a need existsfor new pesticides.

DEFINITIONS

The examples given in the definitions are generally non-exhaustive andmust not be construed as limiting the invention disclosed in thisdocument. It is understood that a substituent should comply withchemical bonding rules and steric compatibility constraints in relationto the particular molecule to which it is attached.

“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbondouble bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.

“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygensingle bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

“Alkoxy” means an alkyl further consisting of a carbon-oxygen singlebond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy,isobutoxy, and tert-butoxy.

“Alkyl” means an acyclic, saturated, branched or unbranched, substituentconsisting of carbon and hydrogen, for example, methyl, ethyl, (C₃)alkylwhich represents n-propyl and isopropyl), (C₄)alkyl which representsn-butyl, sec-butyl, isobutyl, and tert-butyl.

“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbontriple bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.

“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygensingle bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, andoctynyloxy.

“Aryl” means a cyclic, aromatic substituent consisting of hydrogen andcarbon, for example, phenyl, naphthyl, and biphenyl.

“(C_(x)-C_(y))” where the subscripts “x” and “y” are integers such as 1,2, or 3, means the range of carbon atoms for a substituent—for example,(C₁-C₄)alkyl means methyl, ethyl, n-propyl, isopropyl, n-butyl,sec-butyl, isobutyl, and tert-butyl, each individually.

“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at leastone carbon-carbon double bond) substituent consisting of carbon andhydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl,norbornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl,hexahydronaphthyl, and octahydronaphthyl.

“Cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“Cycloalkyl” means a monocyclic or polycyclic, saturated substituentconsisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl,cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygensingle bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,norbornyloxy, and bicyclo[2.2.2]octyloxy.

“Halo” means fluoro, chloro, bromo, and iodo.

“Haloalkoxy” means an alkoxy further consisting of, from one to themaximum possible number of identical or different, halos, for example,fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy,trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.

“Haloalkyl” means an alkyl further consisting of, from one to themaximum possible number of, identical or different, halos, for example,fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl,trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

“Heterocyclyl” means a cyclic substituent that may be fully saturated,partially unsaturated, or fully unsaturated, where the cyclic structurecontains at least one carbon and at least one heteroatom, where saidheteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, thatatom can be in other oxidation states such as a sulfoxide and sulfone.Examples of aromatic heterocyclyls include, but are not limited to,benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl,benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl,indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl,quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl,triazinyl, and triazolyl. Examples of fully saturated heterocyclylsinclude, but are not limited to, piperazinyl, piperidinyl, morpholinyl,pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl andtetrahydropyranyl. Examples of partially unsaturated heterocyclylsinclude, but are not limited to, 1,2,3,4-tetrahydroquinolinyl,4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl,and 2,3-dihydro-[1,3,4]-oxadiazolyl. Additional examples include thefollowing

DETAILED DESCRIPTION

This document discloses molecules having the following formula (“FormulaOne”):

wherein

(a) A is either

(b) R1 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C₁-C₆alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted orunsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substitutedor unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstitutedC₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9,C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9,S(O)_(n)OR9, S(O)_(n)N(R9)₂, or R9S(O)_(n)R9,

-   -   wherein each said R1, which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl, (each of        which that can be substituted, may optionally be substituted        with R9);

(c) R2 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C₁-C₆alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted orunsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substitutedor unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstitutedC₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9,C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9,S(O)_(n)OR9, or R9S(O)_(n)R9,

-   -   wherein each said R2, which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl, (each of        which that can be substituted, may optionally be substituted        with R9);

(d) R3 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C₁-C₆alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted orunsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substitutedor unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstitutedC₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9,C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9,S(O)_(n)OR9, or R9S(O)_(n)R9,

-   -   wherein each said R3, which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl, (each of        which that can be substituted, may optionally be substituted        with R9);

(e) when A is

-   -   (1) A1 then A1 is either        -   (a) A11

-   -   -   -   where R4 is H, NO₂, substituted or unsubstituted C₁-C₆                alkyl, substituted or unsubstituted C₂-C₆ alkenyl,                substituted or unsubstituted C₁-C₆ alkoxy, substituted                or unsubstituted C₃-C₁₀ cycloalkyl, substituted or                unsubstituted C₃-C₁₀ cycloalkenyl, substituted or                unsubstituted C₆-C₂₀ aryl, substituted or unsubstituted                C₁-C₂₀ heterocyclyl, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂,                N(R9)₂, N(R9)C(═X1)R9, S(O)_(n)OR9, or R9S(O)_(n)R9,

        -   wherein each said R4, which is substituted, has one or more            substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆            alkyl, C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl,            C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl,            C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀            halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀            heterocyclyl, (each of which that can be substituted, may            optionally be substituted with R9), or

        -   (b) A12

-   -   -   -   where R4 is a C₁-C₆ alkyl,

    -   (2) A2 then R4 is H, F, Cl, Br, I, CN, NO₂, substituted or        unsubstituted C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆        alkenyl, substituted or unsubstituted C₁-C₆ alkoxy, substituted        or unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted        C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀        cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl,        substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9, C(═X1)R9,        C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9,        S(O)_(n)OR9, or R9S(O)_(n)R9,        -   wherein each said R4, which is substituted, has one or more            substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆            alkyl, C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl,            C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl,            C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀            halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀            heterocyclyl, (each of which that can be substituted, may            optionally be substituted with R9);

(f) R5 is H, F, Cl, Br, I, CN, NO₂, substituted or unsubstituted C₁-C₆alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted orunsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substitutedor unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstitutedC₆-C₂₀ aryl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, or R9S(O)_(n)R9,

-   -   wherein each said R5, which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        OR9, S(O)_(n)OR9, or C₆-C₂₀ aryl, (each of which that can be        substituted, may optionally be substituted with R9);

(g)

-   -   (1) when A is A1 then R6 is substituted or unsubstituted C₁-C₆        alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted        or unsubstituted C₁-C₆ alkoxy, substituted or unsubstituted        C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀        cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl,        substituted or unsubstituted C₆-C₂₀ aryl, substituted or        unsubstituted C₁-C₂₀ heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9,        C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9, S(O)_(n)OR9,        R9S(O)_(n)R9, C₁-C₆ alkyl C₆-C₂₀ aryl (wherein the alkyl and        aryl can independently be substituted or unsubstituted),        C(═X2)R9, C(═X1)X2R9, R9X2C(═XOR9, R9X2R9, C(═O)(C₁-C₆        alkyl)S(O)_(n)(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆        alkyl), (C₁-C₆ alkyl)OC(═O)(C₆-C₂₀ aryl), (C₁-C₆        alkyl)OC(═O)(C₁-C₆ alkyl), C₁-C₆ alkyl-(C₃-C₁₀ cyclohaloalkyl),        or (C₁-C₆ alkenyl)C(═O)O(C₁-C₆ alkyl), or R9X2C(═X1)X2R9,        -   wherein each said R6, which is substituted, has one or more            substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆            alkyl, C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl,            C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl,            C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀            halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀            heterocyclyl, R9aryl, (each of which that can be            substituted, may optionally be substituted with R9),        -   optionally R6 and R8 can be connected in a cyclic            arrangement, where optionally such arrangement can have one            or more heteroatoms selected from O, S, or, N, in the cyclic            structure connecting R6 and R8, and    -   (2) when A is A2 then R6 is H, substituted or unsubstituted        C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆ alkenyl,        substituted or unsubstituted C₁-C₆ alkoxy, substituted or        unsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted        C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀        cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl,        substituted or unsubstituted C₁-C₂₀ heterocyclyl, OR9, C(═X1)R9,        C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂, N(R9)C(═X1)R9, SR9,        S(O)_(n)OR9, R9S(O)_(n)R9, C₁-C₆ alkyl C₆-C₂₀ aryl (wherein the        alkyl and aryl can independently be substituted or        unsubstituted), C(═X2)R9, C(═X1)X2R9, R9X2C(═X1)R9, R9X2R9,        C(═O)(C₁-C₆ alkyl)S(O)_(n)(C₁-C₆ alkyl), C(═O)(C₁-C₆        alkyl)C(═O)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)OC(═O)(C₆-C₂₀ aryl),        (C₁-C₆ alkyl)OC(═O)(C₁-C₆ alkyl), C₁-C₆ alkyl-(C₃-C₁₀        cyclohaloalkyl), or (C₁-C₆ alkenyl)C(═O)O(C₁-C₆ alkyl), or        R9X2C(═X1)X2R9,        -   wherein each said R6, which is substituted, has one or more            substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆            alkyl, C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl,            C₁-C₆ haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl,            C₃-C₁₀ cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀            halocycloalkenyl, OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀            heterocyclyl, R9aryl, (each of which that can be            substituted, may optionally be substituted with R9),        -   optionally R6 and R8 can be connected in a cyclic            arrangement, where optionally such arrangement can have one            or more heteroatoms selected from O, S, or N, in the cyclic            structure connecting R6 and R8;

(h) R7 is O, S, NR9, or NOR9;

(i) R8 is substituted or unsubstituted C₁-C₆ alkyl, substituted orunsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₁-C₆ alkoxy,substituted or unsubstituted C₂-C₆ alkenyloxy, substituted orunsubstituted C₃-C₁₀ cycloalkyl, substituted or unsubstituted C₃-C₁₀cycloalkenyl, substituted or unsubstituted C₆-C₂₀ aryl, substituted orunsubstituted C₁-C₂₀ heterocyclyl OR9, OR9S(O)_(n)R9, C(═X1)R9,C(═X1)OR9, R9C(═X1)OR9, R9X2C(═X1)R9X2R9, C(═X1)N(R9)₂, N(R9)₂,N(R9)(R9S(O)_(n)R9), N(R9)C(═X1)R9, SR9, S(O)_(n)OR9, R9S(O)_(n)R9, orR9S(O)_(n)(NZ)R9,

-   -   wherein each said R8, which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        N(R9)S(O)_(n)R9, oxo, OR9, S(O)_(n)OR9, R9S(O)_(n)R9,        S(O)_(n)R9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl, (each of which        that can be substituted, may optionally be substituted with R9);

(j) R9 is (each independently) H, CN, substituted or unsubstituted C₁-C₆alkyl, substituted or unsubstituted C₂-C₆ alkenyl, substituted orunsubstituted C₁-C₆ alkoxy, substituted or unsubstituted C₂-C₆alkenyloxy, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substitutedor unsubstituted C₃-C₁₀ cycloalkenyl, substituted or unsubstitutedC₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀ heterocyclyl,S(O)_(n)C₁-C₆ alkyl, N(C₁-C₆alkyl)₂,

-   -   wherein each said R9, which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        OC₁-C₆ alkyl, OC₁-C₆ haloalkyl, S(O)_(n)C₁-C₆alkyl,        S(O)_(n)OC₁-C₆ alkyl, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl;

(k) n is 0, 1, or 2;

(l) X is N or CR_(n1) where R_(n1) is H, F, Cl, Br, I, CN, NO₂,substituted or unsubstituted C₁-C₆ alkyl, substituted or unsubstitutedC₂-C₆ alkenyl, substituted or unsubstituted C₁-C₆ alkoxy, substituted orunsubstituted C₂-C₆ alkenyloxy, substituted or unsubstituted C₃-C₁₀cycloalkyl, substituted or unsubstituted C₃-C₁₀ cycloalkenyl,substituted or unsubstituted C₆-C₂₀ aryl, substituted or unsubstitutedC₁-C₂₀ heterocyclyl, OR9, C(═X1)R9, C(═X1)OR9, C(═X1)N(R9)₂, N(R9)₂,N(R9)C(═X1)R9, SR9, S(O)_(n)R9, S(O)_(n)OR9, or R9S(O)_(n)R9,

-   -   wherein each said R_(n1) which is substituted, has one or more        substituents selected from F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl,        C₂-C₆ alkenyl, C₁-C₆ haloalkyl, C₂-C₆ haloalkenyl, C₁-C₆        haloalkyloxy, C₂-C₆ haloalkenyloxy, C₃-C₁₀ cycloalkyl, C₃-C₁₀        cycloalkenyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ halocycloalkenyl,        OR9, S(O)_(n)OR9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl, (each of        which that can be substituted, may optionally be substituted        with R9);

(m) X1 is (each independently) O or S;

(n) X2 is (each independently) O, S, ═NR9, or ═NOR9; and

(o) Z is CN, NO₂, C₁-C₆ alkyl(R9), C(═X1)N(R9)₂; and

(p) with the following provisos

-   -   (1) that R6 and R8 cannot both be C(═O)CH₃,    -   (2) that when A1 is A11 then R6 and R8 together do not form        fused ring systems,    -   (3) that R6 and R8 are not linked in a cyclic arrangement with        only —CH₂—,    -   (4) that when A is A2 then R5 is not C(═O)OH,    -   (5) that when A is A2 and R6 is H then R8 is not a —(C₁-C₆        alkyl)-β-(substituted aryl), and    -   (6) that when A is A2 then R6 is not —(C₁alkyl)(substituted        aryl).

In another embodiment of this invention A is A1.

In another embodiment of this invention A is A2.

In another embodiment of this invention R1 is H.

In another embodiment of this invention R2 is H.

In another embodiment of this invention R3 is selected from H, orsubstituted or unsubstituted C₁-C₆ alkyl.

In another embodiment of this invention R3 is selected from H or CH₃.

In another embodiment of the invention when A is A1 then A1 is A11.

In another embodiment of the invention when A is A1, and A1 is A11, thenR4 is selected from H, or substituted or unsubstituted C₁-C₆ alkyl, orsubstituted or unsubstituted C₆-C₂₀ aryl.

In another embodiment of the invention when A is A1, and A1 is A11 thenR4 is selected from CH₃, CH(CH₃)₂, or phenyl.

In another embodiment of the invention when A is A1, and A1 is A12, thenR4 is CH₃.

In another embodiment of this invention when A is A2 then R4 is selectedfrom H, or substituted or unsubstituted C₁-C₆ alkyl, substituted orunsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C₁₀cycloalkyl, substituted or unsubstituted C₆-C₂₀ aryl, wherein each saidR4, which is substituted, has one or more substituents selected from F,Cl, Br, or I.

In another embodiment of this invention when A is A2 then R4 is H orC₁-C₆ alkyl.

In another embodiment of this invention when A is A2 then R4 is H, CH₃,CH₂CH₃, CH═CH₂, cyclopropyl, CH₂Cl, CF₃, or phenyl.

In another embodiment of this invention when A is A2 then R4 is Cl.

In another embodiment of this invention R5 is H, F, Cl, Br, I, orsubstituted or unsubstituted C₁-C₆ alkyl, substituted or unsubstitutedC₁-C₆ alkoxy.

In another embodiment of this invention R5 is H, OCH₂CH₃, F, Cl, Br, orCH₃.

In another embodiment of this invention, when A is A1 then R6 issubstituted or unsubstituted C₁-C₆ alkyl.

In another embodiment of this invention when A is A2 then R6 is selectedfrom is substituted or unsubstituted C₁-C₆ alkyl, substituted orunsubstituted C₂-C₆ alkenyl, substituted or unsubstituted C₃-C₁₀cycloalkyl, C(═X1)R9, C(═X1)X2R9, R9X2R9, C(═O)(C₁-C₆alkyl)S(O)_(n)(C₁-C₆ alkyl), (C₁-C₆ alkyl)OC(═O)(C₆-C₂₀ aryl), (C₁-C₆alkyl)OC(═O)(C₁-C₆ alkyl), or R9X2C(═X1)X2R9.

In another embodiment of this invention when A is A2 then R6 and R8 areconnected in a cyclic arrangement, where optionally such arrangement canhave one or more heteroatoms selected from O, S, or, N, in the cyclicstructure connecting R6 and R8.

In another embodiment of this invention R6 is C₁-C₆ alkyl, or C₁-C₆alkyl-phenyl.

In another embodiment of this invention R6 is H, CH₃, CH₂CH₃, CH₂CH₂CH₃,CH(CH₃)₂, CH₂-phenyl, CH₂CH(CH₃)₂, CH₂cyclopropyl, C(═O)CH₂CH₂SCH₃,C(═O)OC(CH₃)₃, CH₂CH═CH₂, C(═O)OCH₂CH₃, C(═O)CH(CH₃)CH₂SCH₃,cyclopropyl, CD₃, CH₂OC(═O)phenyl, C(═O)CH₃, C(═O)CH(CH₃)₂,CH₂C(═O)CH(CH₃)₂, CH₂C(═O)CH₃, C(═O)phenyl, CH₂OCH₃, CH₂C(═O)CH₂OCH₂CH₃,CH₂CH₂OCH₃, CH₂C(═O)OCH(CH₃)₂, CH₂CH₂OCH₂OCH₃, CH₂CH₂OCH₃,CH₂CH₂C(═O)CH₃, CH₂CN.

In another embodiment of this invention R6 is methyl or ethyl.

In another embodiment of this invention R7 is O or S.

In another embodiment of this invention R8 is selected from substitutedor unsubstituted C₁-C₆ alkyl, substituted or unsubstituted C₂-C₆alkenyl, substituted or unsubstituted C₃-C₁₀ cycloalkyl, substituted orunsubstituted C₆-C₂₀ aryl, substituted or unsubstituted C₁-C₂₀heterocyclyl, R9C(═X1)OR9, SR9, S(O)_(n)OR9, R9S(O)_(n)R9, orR9S(O)_(n)(NZ)R9.

In another embodiment of this invention R8 is CH(CH₃)CH₂SCH₃, CH(CH₃)₂,C(CH₃)₂CH₂SCH₃, CH₂CH₂SCH₃, CH₂CF₃, CH₂CH₂C(═O)OCH₃, N(H)(CH₂CH₂SCH₃),OCH₂CH₂SCH₃, CH(CH₂SCH₃)(CH₂-phenyl), thiazolyl, oxazolyl, isothiazolyl,substituted-furanyl, CH₃, C(CH₃)₃, phenyl, CH₂CH₂OCH₃, pyridyl,CH₂CH(CH₃)SCH₃, OC(CH₃)₃, C(CH₃)₂CH₂SCH₃, CH(CH₃)CH(CH₃)SCH₃,CH(CH₃)CF₃, CH₂CH₂-thienyl, CH(CH₃)SCF₃, CH₂CH₂Cl, CH₂CH₂CH₂CF₃,CH₂CH₂S(═O)CH₃, CH(CH₃)CH₂S(═O)CH₃, CH₂CH₂S(═O)₂CH₃,CH(CH₃)CH₂S(═O)₂CH₃, NCH₂CH₃, N(H)(CH₂CH₂CH₃), C(CH₃)═C(H)(CH₃),N(H)(CH₂CH═CH₂), CH₂CH(CF₃)SCH₃, CH(CF₃)CH₂SCH₃, thietanyl, CH₂CH(CF₃)₂,CH₂CH₂CF(OCF₃)CF₃, CH₂CH₂CF(CF₃)CF₃, CF(CH₃)₂, CH(CH₃)phenyl-Cl,CH(CH₃)phenyl-F, CH(CH₃)phenyl-OCF₃, CH₂N(CH₃)(S(═O)₂N(CH₃)₂,CH(CH₃)OCH₂CH₂SCH₃, CH(CH₃)OCH₂CH₂OCH₃, OCH₃, CH(CH₃)SCH₃, CH₂SCH₃,N(H)CH₃, CH(Br)CH₂Br, or CH(CH₃)CH₂SCD₃.

In another embodiment of this invention R8 is selected from (substitutedor unsubstituted C₁-C₆ alkyl)-S(O)_(n)-(substituted or unsubstitutedC₁-C₆ alkyl) wherein said substituents on said substituted alkyls areselected from F, Cl, Br, I, CN, NO₂, N(R9)S(O)_(n)R9, OR9, S(O)_(n)OR9,R9S(O)_(n)R9, S(O)_(n)R9, C₆-C₂₀ aryl, or C₁-C₂₀ heterocyclyl, (each ofwhich that can be substituted, may optionally be substituted with R9).

In another embodiment of this invention X is CR_(n1) where R_(n1) is Hor halo.

In another embodiment of this invention X is CR_(n1) where R_(n1) is Hor F.

In another embodiment of this invention X1 is O.

In another embodiment of this invention X2 is O.

While these embodiments have been expressed, combinations of theseembodiments are envisioned. Furthermore, other embodiments, andcombinations of these expressed embodiments and other embodiments arepossible.

The molecules of Formula One will generally have a molecular mass ofabout 100 Daltons to about 1200 Daltons. However, it is generallypreferred if the molecular mass is from about 120 Daltons to about 900Daltons, and it is even more generally preferred if the molecular massis from about 140 Daltons to about 600 Daltons.

The following schemes illustrate approaches to generatingaminopyrazoles. In step a of Scheme I, treatment of a 3-acetopyridine ora 5-acetopyrimidine of Formula II, wherein R1, R2, R3 and X are aspreviously defined, with carbon disulfide and iodomethane in thepresence of a base such as sodium hydride and in a solvent such asdimethyl sulfoxide provides the compound of Formula III. In step b ofScheme I, the compound of Formula III can be treated with an amine oramine hydrochloride, in the presence of a base, such as triethylamine,in a solvent such as ethyl alcohol to afford the compound of Formula IV,wherein R1, R2, R3, R6 and X are as previously defined. The compound ofFormula IV can be transformed into the aminopyrazole of Formula Va whereR5=H as in step c of Scheme I and as in Peruncheralathan, S. et al. J.Org. Chem. 2005, 70, 9644-9647, by reaction with a hydrazine, such asmethylhydrazine, in a polar protic solvent such as ethyl alcohol.

Another approach to aminopyrazoles is illustrated in Scheme II. In stepa, the nitrile of Formula VI wherein X, R1, R2 and R3 are as previouslydefined and R5 is hydrogen, is condensed as in Dhananjay, B. Kendre etal. J. Het Chem 2008, 45, (5), 1281-86 with hydrazine of Formula VII,such as methylhydrazine to give a mixture of aminopyrazoles of FormulaVb, wherein R5 and R6=H, both of whose components were isolated.

Preparation of Aminopyrazoles Such as Those of Formula XIIa isDemonstrated in Scheme III. The compound of Formula X in step a and asin Cristau, Henri-Jean et al. Eur. J. Org. Chem. 2004, 695-709 can beprepared through the N-arylation of a pyrazole of Formula IX with anappropriate aryl halide of Formula VIIIa where Q is bromo in thepresence of a base such as cesium carbonate, a copper catalyst such ascopper (II) oxide and a ligand such as salicylaldoxime in a polaraprotic solvent such as acetonitrile. Compounds of Formula IX, as shownin Scheme III, wherein R4=Cl and R5=H, can be prepared as in Pelcman, B.et al WO 2007/045868 A1. Nitration of the pyridylpyrazole of Formula Xas in step b of Scheme III and as in Khan, Misbanul Ain et al. J.Heterocyclic Chem. 1981, 18, 9-14 by reaction with nitric acid andsulfuric acid gave compounds of Formula XIa. Reduction of the nitrofunctionality of compounds of Formula XIa in the presence of hydrogenwith a catalyst such as 5% Pd/C in a polar aprotic solvent such astetrahydrofuran gave the amine of Formula XIIa, as shown in step c inScheme III. Reduction of the nitro functionality of compounds of FormulaXIa, wherein R1, R2, R3, R4 and X are as previously defined and R5=H, inthe presence of hydrogen with a catalyst such as 10% Pd/C in a polarprotic solvent such as ethanol gave the amine of Formula XIIa, whereinR5=H, as well as the amine of Formula XIIa, wherein R5=OEt, as shown instep d of Scheme III. Compounds of Formula XIa, wherein R1, R2, R3, R5and X are as previously defined and R4=Cl, can be reduced in thepresence of a reducing agent such as iron in a mixture of polar proticsolvents such as acetic acid, water, and ethanol to give amines ofFormula XIIa, wherein R1, R2, R3, R5 and X are as previously definedR4=Cl, as shown in step e of Scheme III. Compounds of Formula XIa,wherein R1, R2, R3, R5 and X are as previously defined and R4=Cl, can beallowed to react under Suzuki coupling conditions with a boronic acidsuch as phenylboronic acid in the presence of a catalyst such aspalladium tetrakis, a base such as 2M aqueous potassium carbonate, andin a mixed solvent system such as ethanol and toluene to providecross-coupled pyrazoles of Formula XIb, as shown in step f of SchemeIII.

In step a of Scheme IV, the compounds of Formula XIIb can be treatedwith triethylorthoformate and an acid such as trifluoroacetic acid.Subsequent addition of a reducing agent such as sodium borohydride in apolar protic solvent such as ethanol gave a compound of Formula XIIIa,wherein R6=methyl.

In step b of Scheme IV, the compound of Formula XIIb can be treated withacetone in a solvent such as isopropyl acetate, an acid such astrifluoroacetic acid and sodium triacetoxyborohydride to give compoundsof Formula XIIIa, wherein R6=isopropyl.

In step c of Scheme IV, the compounds of Formula XIIb can be acylatedwith an acid chloride such as acetyl chloride in a polar aprotic solventsuch as dichloromethane using the conditions described in Scheme V.Reduction of the amide with a reducing agent such as lithium aluminumhydride in a polar aprotic solvent such tetrahydrofuran gives compoundsof Formula XIIIa, wherein R6=ethyl.

Alternatively, in step d of Scheme IV, the compounds of Formula XIIb canbe treated with benzotriazole and an aldehyde in ethanol followed byreduction using, for example, sodium borohydride, to afford compounds ofFormula XIIIa. In step e of Scheme IV, the compounds of Formula XIIb canbe treated with an aldehyde such as propionaldehyde and sodiumtriacetoxyborohydride in a polar aprotic solvent such as dichloromethaneto give compounds of Formula XIIIa, wherein R6=propyl. As in step facylation of compounds of Formula XIIIa in Scheme IV using theconditions described in Scheme IX affords compounds of Formula Ia,wherein R1, R2, R3, R4, R5, R6, R8 and X are as previously defined.

In step a of Scheme V, the compounds of Formula Vc, wherein R1, R2, R3,R4, R5 and R6 and X are as previously defined, can be treated with anacid chloride of Formula XIV, in the presence of a base such astriethylamine or N,N-dimethylaminopyridine in a polar aprotic solventsuch as dichloroethane (DCE) to yield compounds of Formula Ib, whereinR8 is as previously defined. Additionally, when R6=H the 2° amide may besubsequently alkylated in step b of Scheme V with an alkyl halide suchas iodoethane, in the presence of a base such as sodium hydride and apolar aprotic solvent such as N,N-dimethylformamide (DMF) to yield thedesired compounds of Formula Ib. The acid chlorides used in theacylation reactions herein are either commercially available or can besynthesized by those skilled in the art.

In step a of Scheme VI and as in Sammelson et al. Bioorg. Med. Chem.2004, 12, 3345-3355, the aminopyrazoles of Formula Vd, wherein R1, R2,R3, R4, R6 and X are as previously defined and R5=H, can be halogenatedwith a halogen source such as N-chlorosuccinimide or N-bromosuccinimidein a polar aprotic solvent such as acetonitrile to provide theR5-substituted pyrazole. In step b, acylation of this compound using theconditions described in Scheme V affords the compound of Formula Ic,wherein R1, R2, R3, R4, R5, R6, R8 and X are as previously defined.

In step a of Scheme VII, ureas and carbamates are made from theaminopyrazoles of Formula Ve. Compounds of Formula Ve, wherein X, R1,R2, R3, R4, R5 and R6 are as previously defined are allowed to reactwith phosgene to provide the intermediate carbamoyl chloride which issubsequently treated with an amine, as shown in step b, or alcohol, asshown in step c, respectively, to generate a urea of Formula Id or acarbamate of Formula Ie, respectively, wherein R9 is as previouslydefined.

In step a of Scheme VIII, compounds of Formula XIIc, wherein X, R1, R2,R3, R4 and R5 are as previously defined, can be treated withdi-tert-butyl dicarbonate (Boc₂O) and a base such as triethylamine in apolar aprotic solvent such as dichloromethane (DCM) to yield compoundsof Formula XVIa. Treatment of the carbamate functionality with an alkylhalide such as iodomethane or Boc-anhydride in the presence of a basesuch as sodium hydride and in a polar aprotic solvent such as DMF yieldscarbamates of Formula XVII, as shown in step b of Scheme VIII, whereinR6 is as previously defined, except where R6 is hydrogen. The Boc-groupcan be removed under conditions that are well-known in the art, such asunder acidic conditions such as trifluoroacetic acid (TFA) in a polaraprotic solvent like dichloromethane to give compounds of Formula XIIIbas in step c.

In steps a, b and c of Scheme IX, compounds of Formula XIIIc, wherein X,R1, R2, R3, R4, R5 and R6 are as previously defined, can be treated witha compound of Formula XVIII, wherein R8 is as previously defined and R10is either OH, OR9 or O(C═O)OR9, to yield compounds of Formula Id. WhenR10=OH, compounds of Formula XIIIc can be converted to compounds ofFormula Id in the presence of a coupling reagent such as1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl)and a base such as N,N-dimethylaminopyridine (DMAP) in a polar aproticsolvent such as dichloroethane (DCE), as shown in step a. When R10=OR9,compounds of Formula XIIIc can be converted to compounds of Formula Idin the presence of 2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine ina polar aprotic solvent such as 1,4-dioxane under elevated temperature,as shown in step b. When R10=O(C═O)OR9, compounds of Formula XIIIc canbe converted to compounds of Formula Id in a polar aprotic solvent suchas dichloromethane (DCM), as shown in step c. Acylation of amides ofFormula Id, when R6=H, with an acid chloride in the presence of a basesuch as diisopropyl ethylamine in a polar aprotic solvent such asdichloroethane (DCE) yields imides of Formula Ie, as shown in step d.Furthermore, alkylation of amides of Formula Id, when R6=H, with analkyl halide in the presence of a base such as sodium hydride in a polaraprotic solvent such as N,N-dimethylformamide (DMF) yields alkylatedamides of Formula Ie, as shown in step e. Halogenation of compounds ofFormula Id, wherein R1, R2, R3, R4, R6, R8 and X are as previouslydefined and R5=H, with a halogen source such as N-bromosuccinimide in apolar aprotic solvent such as DCE or a halogen source such asN-chlorosuccinimide in a polar aprotic solvent such as DCE oracetonitrile or a halogen source such as Selectfluor® in a mixture ofpolar aprotic solvents such as acetonitrile and DMF give halogenatedpyrazoles of Formula Ie, wherein R5=halogen, as shown in step f ofScheme IX. Amides of Formula Id can be converted to thioamides ofFormula If in the presence of a thionating agent such as Lawesson'sreagent in a polar aprotic solvent such as dichloroethane (DCE), asshown in step g.

In step a of Scheme X, compounds of Formula XIIId, wherein X, R1, R2,R3, R4, R5 and R6 are as previously defined, can be treated withcompounds of Formula XIX, wherein R8 is as previously defined, in apolar aprotic solvent such as dichloroethane (DCE) to yield compounds ofFormula XX. Additionally, when R6=H and R8 contains a halogen, compoundsof Formula XX can be treated with a base, such as sodium hydride, in apolar aprotic solvent, such as THF, to yield compounds of Formula XXI,where m is an integer selected from 1, 2, 3, 4, 5, or 6, as shown instep b of Scheme X.

Oxidation of the sulfide to the sulfoxide or sulfone is accomplished asin Scheme XI where (˜S˜) can be any sulfide previously defined withinthe scope of R8 of this invention. The sulfide of Formula XXIIa, whereinX, R1, R2, R3, R4, R5 and R6 are as previously defined, is treated withan oxidant such as sodium perborate tetrahydrate in a polar proticsolvent such as glacial acetic acid to give the sulfoxide of FormulaXXIII as in step a of Scheme XI. Alternatively, the sulfide of FormulaXXIIa can be oxidized with an oxidant such as hydrogen peroxide in apolar protic solvent such as hexafluoroisopropanol to give the sulfoxideof Formula XXIII as in step d of Scheme XI. The sulfoxide of FormulaXXIII can be further oxidized to the sulfone of Formula XXIV by sodiumperborate tetrahydrate in a polar protic solvent such as glacial aceticacid as in step c of Scheme XI. Alternatively, the sulfone of FormulaXXIV can be generated in a one-step procedure from the sulfide ofFormula XXIIa by using the aforementioned conditions with >2 equivalentsof sodium perborate tetrahydrate, as in step b of Scheme XI.

Oxidation of the sulfide to the sulfoximine is accomplished as in SchemeXII where (˜S˜) can be any sulfide previously defined within the scopeof R8 of this invention. The sulfide of Formula XXIIb, wherein X, R1,R2, R3, R4, R5 and R6 are as previously defined, is oxidized as in stepa with iodobenzene diacetate in the presence of cyanamide in a polaraprotic solvent such as methylene chloride (DCM) to give the sulfilimineof the Formula XXV. The sulfilimine of Formula XXV may be furtheroxidized to the sulfoximine of Formula XXVI with an oxidant such asmeta-Chloroperoxybenzoic acid (“mCPBA”) in the presence of a base suchas potassium carbonate in a protic polar solvent system such as ethanoland water as in step b of Scheme XII.

Iodination of the pyrazole of Formula Xb as in step a of Scheme XIII andas in Potapov, A. et al. Russ. J. Org. Chem. 2006, 42, 1368-1373 wasaccomplished by reaction with an iodinating agent such as iodine in thepresence of acids such as iodic acid and sulfuric acid in a polar proticsolvent such as acetic acid gives compounds of Formula XXVII. In step bof Scheme XIII and as in Wang, D. et al. Adv. Synth. Catal. 2009, 351,1722-1726, aminopyrazoles of Formula XIIIe can be prepared fromiodopyrazoles of Formula XXVII through cross coupling reactions with anappropriate amine in the presence of a base such as cesium carbonate, acopper catalyst such as copper (I) bromide, and a ligand such as1-(5,6,7,8-tetrahydroquinolin-8-yl)ethanone in a polar aprotic solventsuch as DMSO.

In step a of the Scheme XIV, compounds of the formula XXIX, wherein R4is Cl, R5 is H and X⁻ represents Cl⁻, can be prepared according to themethods described in Acta. Pharm. Suec. 22, 147-156 (1985) by Tolf,Bo-Ragnar and Dahlbom, R. In a similar manner, compounds of the FormulaXXIX, wherein R4 is Br, X⁻ represents Br⁻ and R5 is as definedpreviously, can be prepared by treating compounds of the Formula XXVIIIwith hydrogen gas in the presence of a metal catalyst such as 5% Pd onalumina and a solution of 50% aqueous HBr in a solvent such as ethanol.Alternatively, in step a of Scheme XIV, compounds of the Formula XXIX,wherein R4 is Cl or Br, X⁻ represents Cl⁻ or Br⁻ and R5 is as definedpreviously, can be prepared by treating compounds of the Formula XXVIII,wherein R5 is as defined previously, with a hydrosilane such as triethylsilane in the presence of a metal catalyst such as 5% Pd on alumina andan acid such as HCl or HBr, respectively, in a solvent such as ethanol.

In step b of the Scheme XIV, compounds of the Formula XXX, wherein R4 isCl or Br and R5 is as defined previously, can be prepared by treatingthe compounds of the Formula XXIX, wherein R4 is Cl or Br, X⁻ representsCl⁻ or Br⁻ and R5 is as defined previously, with di-tert-butyldicarbonate (Boc₂O) in the presence of a mixture of solvents such as THFand water and a base such as sodium bicarbonate.

In step c of the Scheme XIV, compounds of the Formula XVIa, wherein X,R1, R2, R3 and R5 are as defined previously and R4 is Cl or Br can beobtained by treating compounds of the Formula XXX, wherein R4 is Cl orBr and R5 is as defined previously, with compounds of the Formula VIM,wherein X, R1, R2 and R3 are as defined previously and Q is bromo oriodo, in the presence of a catalytic amount of copper salt such asCuCl₂, an ethane-1,2-diamine derivative such asN¹,N²-dimethylethane-1,2-diamine and a base such as K₃PO₄ in a polaraprotic solvent such as acetonitrile at a suitable temperature.

The Boc-group of compounds of Formula XVIa can be removed underconditions that are well-known in the art such as under acidicconditions such as TFA in a polar aprotic solvent such asdichloromethane to give compounds of Formula XIId, as shown in step d ofScheme XIV.

Bromopyrazoles of Formula XXXI, wherein R1, R2, R3, R5, R8 and X are aspreviously defined, can be allowed to react under Suzuki couplingconditions with a boronic ester such as vinylboronic acid pinacol esteror cyclopropylboronic acid pinacol ester in the presence of a catalystsuch as palladium tetrakis, a base such as 2 M aqueous potassiumcarbonate, and in a mixed solvent system such as ethanol and toluene toprovide compounds of Formula XXXII, as shown in step a of Scheme XV.

The vinyl group of compounds of Formula XXXIII, wherein R1, R2, R3, R5,R6, R8 and X are as previously defined, can be reduced in the presenceof hydrogen with a catalyst such as 10% Pd/C in a polar protic solventsuch methanol to give compounds of Formula XXXIV, as shown in step a ofScheme XVI. Oxidation of the vinyl group of compounds of Formula XXXIIIusing an oxidant such as osmium tetroxide in the presence of sodiumperiodate in mixture of a polar protic solvent such as water and a polaraprotic solvent such as THF gave compounds of Formula XXXV, as shown instep b of Scheme XVI. Reduction of the aldehyde of compounds of FormulaXXXV, as shown in step c of Scheme XVI, with a reducing agent such assodium borohydride in a polar protic solvent such as methanol gave thecorresponding alcohol of Formula XXXVI. Treatment of compounds ofFormula XXXVI with a chlorinating agent such as thionyl chloride in apolar aprotic solvent such as dichloromethane gave compounds of FormulaXXXVII, as shown in step d of Scheme XVI.

In step a of Scheme XVII, an α,β-unsaturated acid XXXVIII can be treatedwith a nucleophile such as sodium thiomethoxide in a polar proticsolvent such as methanol to give acid XXXIX.

EXAMPLES

The examples are for illustration purposes and are not to be construedas limiting the invention disclosed in this document to only theembodiments disclosed in these examples.

Starting materials, reagents, and solvents that were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Stanford Research Systems and are uncorrected. Molecules aregiven their known names, named according to naming programs within ISISDraw, ChemDraw or ACD Name Pro. If such programs are unable to name amolecule, the molecule is named using conventional naming rules. All NMRshifts are in ppm (δ) and were recorded at 300, 400 or 600 MHz unlessotherwise stated.

Example 1 Step 1: Preparation of3,3-bis-methylsulfanyl-1-pyridin-3-yl-propenone

To a room-temperature suspension of sodium hydride (NaH, 60% suspensionin mineral oil; 4.13 g, 86 mmol) in dry dimethyl sulfoxide (DMSO, 60 mL)under an atmosphere of nitrogen (N₂) was added 3-acetylpyridine (5.00 g,41.3 mmol) dropwise over 30 minutes (min) The mixture was stirred for anadditional 30 minutes at the same temperature. Carbon disulfide (CS₂;3.27 g, 43 mmol) was added dropwise with vigorous stirring followed byiodomethane (12.21 g, 86 mmol) dropwise over a period of 45 min Stirringwas continued for an additional 18 hours (h) under N₂. The reaction wasquenched with cold water (H₂O, 50 mL). The dark solid was filtered andwashed with ice-cold ethyl alcohol (EtOH) until the washings werecolorless. The off-white solid product was dried under vacuum at 60° C.to provide 3,3-bis-methylsulfanyl-1-pyridin-3-yl-propenone as a brownsolid (4.8 g, 51%): ¹H NMR (300 MHz, CDCl₃) δ 9.13 (d, J=1.8 Hz, 1H),8.72 (dd, J=4.8, 1.6 Hz, 1H), 8.23 (ddd, J=7.9, 2, 2 Hz, 1H), 7.40 (dd,J=7.9, 4.8 Hz, 1H), 6.73 (s, 1H), 2.58 (d, J=9.4 Hz, 6H); MS m/z 226.2(M+1).

1-(5-fluoropyridin-3-yl)-3,3-bis(methylthio)prop-2-en-1-one was preparedas described in Example 1, Step 1: mp 150-152° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.93 (t, J=1.6 Hz, 1H), 8.58 (d, J=2.8 Hz, 1H), 7.94 (ddd,J=8.9, 2.8, 1.7 Hz, 1H), 6.69 (s, 1H), 2.60 (s, 3H), 2.57 (s, 3H).

Example 1 Step 2: Preparation of(Z)-3-methylamino-3-methylsulfanyl-1-pyridin-3-yl-propenone

A solution of 3,3-bis-methylsulfanyl-1-pyridin-3-yl-propenone (18.6 g,82.5 mmol) in absolute alcohol (400 mL) under N₂ was treated withmethylamine hydrochloride (27.86 g, 412 mmol) followed by triethylamine(Et₃N, 58.5 mL, 412 mmol). The mixture was heated to reflux for 3 h,cooled to room temperature and concentrated under reduced pressure. Thesolid residue was dissolved in ethyl acetate (EtOAc; 150 mL). Thesolution was washed with H₂O (2×50 mL) and brine (50 mL), dried overNa₂SO₄, concentrated under reduced pressure and purified by silica gelchromatography eluting with 10% EtOAc in petroleum ether to yield(Z)-3-methylamino-3-methylsulfanyl-1-pyridin-3-yl-propenone as a paleyellow solid (8.6 g, 50%): ¹H NMR (300 MHz, CDCl₃) δ 11.8 (br s, 1H),9.06 (s, 1H); 8.67 (d, J=3.9 Hz, 1H), 8.26 (d, J=8.0 Hz 1H), 7.46 (dd,J=7.6, 4.9 Hz 1H), 5.62 (s, 1H), 3.10 (d, J=5.2 Hz, 3H), 2.52 (s, 3H);MS (m/z) 209.2 [M+1].

(Z)-3-(ethylamino)-3(methylthio)-1-(pyridin-3-yl)prop-2-en-1-one wasprepared as described in Example 1, Step 2: ¹H NMR (400 MHz, CDCl₃) δ11.81 (bs, 1H), 9.04 (dd, J=2.2, 0.7 Hz, 1H), 8.64 (dd, J=4.8, 1.7 Hz,1H), 8.29-7.98 (m, 1H), 7.35 (ddd, J=7.9, 4.8, 0.9 Hz, 1H), 3.45 (q,J=7.2, 5.6 Hz, 2H), 2.50 (s, 3H), 1.35 (t, J=7.2 Hz, 3H).

(Z)-3-(cyclopropylmethyl)amino-3(methylthio)-1-(pyridin-3-yl)prop-2-en-1-onewas prepared as described in Example 1, Step 2: ¹H NMR (400 MHz, CDCl₃)δ 9.00 (s, 1H), 9.05 (dd, J=2.2, 0.7 Hz, 1H), 8.64 (dd, J=4.8, 1.7 Hz,1H), 8.16 (dt, J=7.9, 2.0 Hz, 1H), 7.35 (ddd, J=7.9, 4.8, 0.8 Hz, 1H),5.62 (s, 1H), 3.27 (dd, J=7.0, 5.5 Hz, 2H), 2.50 (s, 3H), 1.20-1.07 (m,1H), 0.73-0.49 (m, 2H), 0.41-0.17 (m, 2H).

Example 1 Step 3: Preparation ofmethyl-(2-methyl-5-pyridin-3-pyrazol-3-yl)-amine

A solution of(Z)-3-methylamino-3-methylsulfanyl-1-pyridin-3-yl-propenone (3.00 g, 14mmol) and methylhydrazine (729 mg, 15.4 mmol) in absolute EtOH (64 mL)was stirred at reflux for 18 h under N₂, cooled to room temperature andevaporated under reduced pressure. The residue was dissolved in EtOAc(50 mL), and the organic layer was washed with H₂O (2×30 mL) and brine(30 mL), dried over Na₂SO₄, concentrated under reduced pressure andpurified using silica gel chromatography eluting with a gradient of 0-1%EtOH in EtOAc to yield two regioisomers in a 1:2 ratio, with the majorregioisomer as a brown solid (1.0 g, 27%): ¹H NMR (300 MHz, CDCl₃) δ8.97 (d, J=1.3 Hz, 1H), 8.51 (dd, J=3.6, 1.0 Hz, 1H), 8.07 (ddd, J=5.9,1.4, 1.4 Hz, 1H), 7.30 (dd, J=5.9, 3.6 Hz, 1H), 5.82 (s, 1H), 3.69 (s,3H), 2.93 (s, 3H); MS (m/z) 188.6 [M+1].

1-Ethyl-N-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine was prepared asdescribed in Example 1, Step 3: ESIMS m/z 204 ([M+2H]).

N-ethyl-1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine was prepared asdescribed in Example 1, Step 3: ESIMS m/z 203 ([M+H]).

N-methyl-1-phenyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine was prepared asdescribed in Example 1, Step 3: ESIMS m/z 252 ([M+2H]).

N-(cyclopropylmethyl)-1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine wasprepared as described in Example 1, Step 3: ESIMS m/z 230 ([M+2H]).

1-Isopropyl-N-methyl-3-pyridin-3-yl)-1H-pyrazol-5-amine was prepared asdescribed in Example 1, Step 3: ¹H NMR (300 MHz, CDCl₃) δ 8.53 (s, 1H),8.06-7.90 (m, J=7.2 Hz, 2H), 7.13 (dd, J=7.9, 5.6 Hz, 1H), 5.33 (s, 1H),3.70 (bs, 1H), 3.65 (dt, J=13.2, 6.6 Hz, 1H), 2.31 (s, 3H), 0.88 (d,J=6.6 Hz, 6H); ESIMS m/z 217 ([M+H]).

3-(5-Fluoropyridin-3-yl)-N, 1-dimethyl-1H-pyrazol-5-amine was preparedas described in Example 1, Step 3: ¹H NMR (300 MHz, CDCl₃) δ 8.28 (s,1H), 7.87 (t, J=1.3 Hz, 1H), 7.60 (m, 1H), 6.66 (s, 1H), 5.28 (bs, 2H),3.12 (s, 3H), 2.34 (s, 3H); ESIMS m/z 206 ([M+H])

Example 2 Preparation of(4-chloro-2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-methylamine

A mixture of methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine(0.35 g, 1.8 mmol) and N-chlorosuccinimide (0.273 g, 2 mmol) wascombined in acetonitrile (3 mL), stirred at room temperature for 30minutes, concentrated under reduced pressure and purified using silicagel chromatography eluting with a gradient of EtOAc in hexanes to yieldthe title compound as a yellow oil (0.096 g, 23%): IR (thin film) 1581.6cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.12 (d, J=1.5 Hz, 1H), 8.57 (dd, J=4.8,1.3 Hz, 1H), 8.15 (ddd, J=7.8, 2.0, 2.0 Hz, 1H), 7.33 (dd, J=8.1, 5.1Hz, 1H), 3.80 (s, 3H), 2.91 (d, J=5.8 Hz, 3H); ESIMS (m/z) 225.6 [M+2].

The reaction also gave4-chloro-2-methyl-5-pyridin-3-yl-2H-pyrazol-3-ylamine as a green gum(0.046 g, 13%): IR (thin film) 1720.5 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz) δ9.13 (br s, 1H), 8.57 (br s, 1H), 8.16 (dt, J=8.0, 2.0 Hz, 1H), 7.33(dd, J=7.8, 4.8 Hz, 1H), 3.76 (s, 3H); ESIMS (m/z) 207.0 [M−1].

Example 3 Preparation of2,N-dimethyl-N-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-methylsulfanyl-propionamide(Compound 1)

To a solution of methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine(150 mg, 0.8 mmol) under N₂ in ice-cold dichloroethane (DCE; 2 mL) wasadded dropwise via pipette a solution of2-methyl-3-methylsulfanyl-propionylchloride (146 mg, 0.9 mmol) in DCE(1.5 mL). After stirring for 10 minutes (min), a solution of4-N,N-dimethylaminopyridine (DMAP; 107 mg, 0.9 mmol) in DCE (2 mL) wasadded dropwise. The ice bath was removed after 30 min, and the mixturewas stirred at room temperature for 90 min and then at reflux for 14 h.The mixture was concentrated under reduced pressure and was purified bysilica gel chromatography eluting with a gradient of EtOAc in hexane.The product,2,N-dimethyl-N-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-methylsulfanyl-propionamide,was isolated as a yellow semi-solid (44 mg, 24%): ¹H NMR (400 MHz,CDCl₃) δ 9.00 (s, 1H), 8.58 (s, 1H), 8.08 (br d, J=7.0 Hz, 1H), 7.35 (brdd, J=7.3, 4.8 Hz, 1H), 6.58 (br s, 0.5H), 6.49 (br s, 0.5H), 3.89-3.79(m, 3H), 3.25 (s, 3H), 2.96-2.80 (m, 1H), 2.42-2.40 (m, 1H), 2.02-1.99(m, 3H), 2.62 (m, 1H), 1.15 (d, J=6.0 Hz, 3H); MS (m/z) 305.0 [M+1].

Compounds 2-6, 9-10, 12, 18-21, 24-33, 477, 487, 509, 520, 556-557,562-568 were made from the appropriate amines in accordance with theprocedures disclosed in Example 3.

Example 4 Preparation of1-methyl-1-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-(2-methylsulfanyl-ethyl)-urea(Compound 7)

To a solution of methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine(150 mg, 0.8 mmol) in ice-cold DCE (2 mL) under N₂ was added a solutionof phosgene in toluene (20%, 0.43 mL, 0.88 mmol). The ice bath wasremoved after 30 min, and the mixture was stirred at room temperaturefor 1 h and at reflux for 2 h. The mixture was cooled to roomtemperature and then more phosgene (0.86 mL, 1.76 mmol) was added. Themixture was stirred at reflux for 90 min and then cooled in an ice bath.To this was added a solution of 2-methylthioethylamine (80 mg, 0.88mmol) in DCE (2 mL). The ice bath was removed after 10 min, and thereaction mixture was stirred at reflux for 14 h, cooled, and dilutedwith DCE (30 mL). The diluted reaction mixture was washed with saturatedNaHCO₃ (20 mL), dried over MgSO₄, adsorbed onto silica gel and purifiedusing silica gel chromatography eluting with a gradient of methanol indichloromethane to afford1-methyl-1-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-(2-methylsulfanyl-ethyl)-ureaas a yellow gum (14 mg, 6%): ¹H NMR (400 MHz, CDCl₃) δ 8.99 (d, J=1.5Hz, 1H), 8.57 (dd, J=4.8, 1.5 Hz, 1H), 8.08 (ddd, J=8.1, 2.1, 2.1 Hz,1H), 7.34 (dd, J=7.9, 4.8 Hz, 1H), 6.52 (s, 1H), 4.88 (br t, J=5.5 Hz,1H), 3.80 (s, 3H), 3.41 (q, J=6.3 Hz, 2H), 3.24 (s, 3H), 2.61 (t, J=6.3,2H), 2.06 (s, 3H); ESIMS (m/z) 292.2 [M+2].

Compound 8 was made in accordance with the procedures disclosed inExample 4 using 2-(methylthio)ethanol in place of2-methylthioethylamine.

Example 5 Preparation of 1-methyl-5-(pyridin-3-yl)-1H-pyrazol-3-amineand 1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine

To ethanol (8.53 ml) was added 3-oxo-3-(pyridin-3-yl)propanenitrile(0.82 g, 5.61 mmol) and methylhydrazine (0.25 g, 5.61 mmol) and stirredat reflux for 2 hours. The reaction was cooled to room temperature andconcentrated to dryness. The crude material was purified by silica gelchromatography by eluting with 0-20% MeOH/dichloromethane to yield twoproducts—1-methyl-5-(pyridin-3-yl)-1H-pyrazol-3-amine (0.060 g; 6.14%):¹H NMR (300 MHz, CDCl₃) δ 8.72 (s, 1H), 8.53 (d, 1H), 7.76-7.63 (m, 1H),7.43-7.33 (m, 1H), 5.75 (s, 1H), 3.76-3.57 (m, 5H) and1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-amine (0.150 g, 15.35%): ¹H NMR(300 MHz, CDCl₃) δ 8.88 (s, 1H), 8.48 (d, 1H), 7.99 (d, 1H), 7.38-7.07(m, 1H), 585 (s, 1H), 3.80-3.59 (m, 5H).

Example 6 Step 1: Preparation of 3-pyrazol-1-yl-pyridine

To a solution of 3-bromopyridine (5 g, 0.031 mol) in 50 ml ofacetonitrile were added pyrazole (2.6 g, 0.038 mol), Cs₂CO₃ (16.5 g,0.050 mol), Cu₂O (0.226 g, 0.0016 mol), and salicylaldoxime (0.867 g,0.006 mol) under N₂ atmosphere. The reaction mass was refluxed for 24hrs at 80° C. The reaction mass was concentrated and the crude waspurified by column chromatography using ethyl acetate and hexane (1:1)to afford the pyrazolyl pyridine as a dark brown liquid (2 g, 43%): ¹HNMR (400 MHz, CDCl₃) δ 8.99 (d, J=2.8 Hz, 1H), 8.48 (dd, J=4.8, 1.2 Hz,1H), 8.11-8.08 (m, 1H), 7.99 (d, J=1.2 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H),7.38-7.35 (m, 1H), 6.53 (t, J=1.2 Hz, 1H); MS (m/z) 146 [M+1].

3-(3-chloro-1H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step1: mp 98-106° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.93 (d, J=2.6 Hz, 1H), 8.57(dd, J=4.8, 1.4 Hz, 1H), 8.03 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.90 (d,J=2.5 Hz, 1H), 7.42 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 6.46 (d, J=2.5 Hz,1H); ¹³C (DMSO-d₆) 148, 142, 140, 136, 131, 126, 125, 108.

2-methyl-3-(3-methyl-1H-pyrazol-1-yl)pyridine was prepared as in Example6, Step 1: ¹H NMR (400 MHz, CDCl₃) δ 8.53 (d, J=4.7 Hz, 1H), 7.67 (d,J=7.9 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.27-7.19 (m, 1H), 6.27 (d, J=1.4Hz, 1H), 2.53 (s, 3H), 2.38 (s, 3H).

3-(3-(Trifluoromethyl)-1H-pyrazol-1-yl)pyridine was prepared from theappropriate starting materials as described in Example 6, Step 1: mp59.0-61.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.00 (s, 1H), 8.70-8.59 (m,1H), 8.11 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 8.05-7.98 (m, 1H), 7.46 (dd,J=8.3, 4.8 Hz, 1H), 6.79 (d, J=2.4 Hz, 1H); EIMS m/z 213.

3-Fluoro-5-(3-methyl-1H-pyrazol-1-yl)pyridine was prepared from theappropriate starting materials as described in Example 6, Step 1: mp70.0-72.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.76-8.73 (m, 1H), 8.37-8.33(m, 1H), 7.88-7.85 (m, 1H), 7.84-7.79 (m, 1H), 6.34-6.29 (m, 1H), 2.37(s, 3H); EIMS m/z 177.

3-(3-Chloro-1H-pyrazol-1-yl)-5-fluoropyridine was prepared from theappropriate starting materials as described in Example 6, Step 1: mp77.0-82.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.75 (d, J=1.8 Hz, 1H), 8.43(d, J=2.3 Hz, 1H), 7.92 (d, J=2.6 Hz, 1H), 7.84 (dt, J=9.3, 2.4 Hz, 1H),6.48 (d, J=2.6 Hz, 1H); EIMS m/z 198.

3-(3-methyl-1H-pyrazol-1-yl)pyridine was prepared as described inExample 6, Step 1: ¹H NMR (400 MHz, CDCl₃) δ 8.94 (bs, 1H), 8.51 (d,J=3.9 Hz, 1H), 8.02 (ddd, J=8.3, 2.6, 1.5 Hz, 1H), 7.90-7.79 (m, 1H),7.39 (dd, J=8.2, 5.1 Hz, 1H), 6.30 (d, J=2.4 Hz, 1H), 2.39 (s, 3H).

3-(5-methyl-1H-pyrazol-1-yl)pyridine was prepared as in Example 6, Step1: ¹H NMR (400 MHz, CDCl₃) δ 8.77 (d, J=2.5 Hz, 1H), 8.65 (dd, J=4.8,1.5 Hz, 1H), 7.84 (ddd, J=8.2, 2.5, 1.5 Hz, 1H), 7.63 (d, J=1.6 Hz, 1H),7.44 (ddd, J=8.2, 4.8, 0.7 Hz, 1H), 6.225 (dd, J=1.6, 0.7 Hz, 1H), 2.40(s, 3H).

Example 6 Step 2: Preparation of 3-(4-nitro-pyrazol-1-yl)-pyridine

3-Pyrazol-1-yl-pyridine (2 g, 0.032 mol) was dissolved in concentratedH₂SO₄ (32 mL 0.598 mmol) and cooled to −5° C. using an ice bath. To thereaction mass, a 1:1 mixture of concentrated HNO₃ (30 mL, 0.673 mmol)and concentrated H₂SO₄ (30 ml, 15 Vol.) was added dropwise over a periodof 30 min. Cooling was discontinued and the reaction mixture was stirredat room temperature overnight. After the reaction was complete, themixture was poured over crushed ice and neutralized with saturatedNaHCO₃, filtered, washed with water and dried to furnish the nitropyrazole as pale yellow solid (1.8 g, 68%): ¹H NMR (400 MHz, DMSO-d₆) δ9.03 (d, J=2.8 Hz, 1H); 8.70 (dd, J=4.8, 1.6 Hz, 1H), 8.69 (s, 1H), 8.33(s, 1H), 8.11-8.08 (m, 1H), 7.51 (dd, J=8.4, 4.8 Hz, 1H); MS (m/z) 191[M+1].

3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example6, Step 2: mp 139-142° C., ¹H NMR (400 MHz, CDCl₃) δ 9.01 (d, J=2.0 Hz,1H), 8.73 (d, J=4.9 Hz, 2H), 8.08 (ddd, J=8.3, 2.5, 1.3 Hz, 1H), 7.52(dd, J=8.3, 4.8 Hz, 1H), EIMS m/z 224.

3-(5-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example6, Step 2: ¹H NMR (400 MHz, CDCl₃) δ 8.81-8.71 (m, 2H), 8.32 (s, 1H),7.83 (ddd, J=8.2, 2.5, 1.6 Hz, 1H), 7.54 (dd, J=8.2, 4.8 Hz, 1H), 2.72(s, 3H).

2-methyl-3-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as inExample 6, Step 2: ¹H NMR (400 MHz, d₆-DMSO) δ 14.01 (s, 1H), 9.37 (d,J=4.0 Hz, 1H), 8.69 (t, J=17.3 Hz, 1H), 8.21 (dd, J=7.7, 4.8 Hz, 1H),2.29 (s, 3H), 2.20 (s, 3H); ¹³C 154, 150, 146, 135, 134.9, 134.8, 134.3,122, 21, 14; EIMS m/z 218.

3-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared as in Example6, Step 2: mp 122-124° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.01 (d, J=2.5 Hz,1H), 8.77-8.56 (m, 2H), 8.07 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.56-7.37(m, 1H), 2.66 (s, 3H); EIMS m/z 208.

3-Fluoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine was prepared fromthe appropriate starting material as described in Example 6, Step 2: mp90.0-92.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.82 (d, J=2.0 Hz, 1H), 8.69(s, 1H), 8.54 (d, J=2.5 Hz, 1H), 7.89 (dt, J=8.9, 2.4 Hz, 1H), 2.66 (s,3H); EIMS m/z 222.

3-(4-Nitro-3-(trifluoromethyl)-1H-pyrazol-1-yl)pyridine was preparedfrom the appropriate starting material as described in Example 6, Step2: mp 121.0-123.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.04 (d, J=2.5 Hz, 1H),8.79 (s, 1H), 8.77 (d, J=0.9 Hz, 1H), 8.13 (ddd, J=8.3, 2.7, 1.4 Hz,1H), 7.55 (dt, J=10.8, 5.4 Hz, 1H); EIMS m/z 258.

3-(3-Chloro-4-nitro-1H-pyrazol-1-yl)-5-fluoropyridine was prepared fromthe appropriate starting material as described in Example 6, Step 2: mp109.5-111.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.83 (d, J=2.1 Hz, 1H), 8.75(s, 1H), 8.60 (d, J=2.4 Hz, 1H), 7.89 (dt, J=8.6, 2.4 Hz, 1H); EIMS m/z242.

3-(3-Bromo-4-nitro-1H-pyrazol-1-yl)pyridine was prepared from theappropriate starting material as described in Example 6, Step 2: mp139.0-141.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.01 (d, J=2.5 Hz, 1H), 8.73(dd, J=4.7, 1.1 Hz, 1H), 8.71 (s, 1H), 8.15-8.00 (m, 1H), 7.52 (dd,J=8.3, 4.8 Hz, 1H); ESIMS m/z 271 ([M+2]⁺).

Example 6 Step 3: Preparation of 1-pyridin-3-yl-1H-pyrazol-4-ylamine

To a solution of 3-(4-nitro-pyrazol-1-yl)-pyridine (1.8 g, 0.009 mol) indry THF (18 ml) was added 5% Pd/C (180 mg) under nitrogen atmosphere.The mixture was then stirred under hydrogen atmosphere until thereaction was complete. The reaction mixture was filtered through a padof celite, and concentrated to dryness to give an impure dark brownsolid (1.76 g): ¹H NMR (400 MHz, DMSO-d₆) δ 8.89 (dd, J=2.8. 0.4 Hz,1H); 8.48 (dd, J=4.8, 1.2 Hz, 1H), 7.99-7.96 (m, 1H), 7.54 (d, J=1.2 Hz,1H), 7.45 (d, J=0.4 Hz, 1H), 7.38-7.35 (m, 1H), 4.81 (bs 1H); ESIMS(m/z) 161 [M+1].

5-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as in Example6, Step 3: ¹H NMR (400 MHz, CDCl₃) δ 8.74 (d, J=2.3 Hz, 1H), 8.63-8.50(m, 1H), 7.81 (ddd, J=8.2, 2.5, 1.5 Hz, 1H), 7.46-7.33 (m, 2H), 2.64(bs, 1H), 2.29 (s, 3H); ¹³C (DMSO-d₆) 147, 144, 137, 133, 130, 129, 124,123, 10; EIMS m/z 174

3-methyl-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as inExample 6, Step 3: mp 211-215° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.10-8.87(m, 3H), 7.51 (s, 1H), 3.24 (bs, 2H), 2.29 (s, 3H); ESIMS m/z 176([M+H]).

3-chloro-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as inExample 6, Step 3: mp 146-148° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.07 (s,1H), 9.02 (s, 2H), 7.52 (s, 1H), 3.45 (s, 2H); ESIMS m/z 196 ([M+H]).

Example 7 Preparation of methyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine

Method A:

To a 25 ml round bottom flask containing1-pyridin-3-yl-1H-pyrazol-4-ylamine (1.76 g, 0.011 mol) in ethanol (26.4ml) was added benzotriazole (1.31 g, 0.011 mol). The reaction was cooledto 0° C.-10° C. and formaldehyde (0.36 mL, 0.0121 mol) was added slowlyand kept for 30 min at this temperature. The reaction was filtered andconcentrated to dryness. The crude material (2.56 g, 0.009 mol) wasdissolved in dry tetrahydrofuran (25.6 mL), cooled to 0° C. and sodiumborohydride (0.326 g, 0.00882 mol.) was added over 15 min. The reactionwas warmed to room temperature and stirred for 2 hours. The reaction waspoured into water and extracted using dichloromethane, the organic layerwas dried over anhydrous Na₂SO₄ and concentrated to dryness. Purifiedthe crude material by silica gel chromatography eluting with 20%methanol/chloroform to afford the desired product as a brown solid(0.610 g, 32%): ¹H NMR (400 MHz, d₆-DMSO) δ 8.92 (d, J=2.4 Hz, 1H), 8.47(dd, J=4.8, 1.6 Hz, 1H), 8.01-7.98 (m, 1H), 7.45 (s, 1H), 7.30 (s, 1H),7.37 (dd, J=8.0, 4.4 Hz, 1H), 2.84 (s, 3H); ESIMS m/z 175 ([M+1]).

Method B:

1-pyridin-3-yl-1H-pyrazol-4-ylamine (1.0 g, 6.2 mmol) was dissolved intriethyl orthoformate (5 ml, 30 mmol) and to that was addedtrifluoroacetic acid (3-4 drops). The reaction mixture was refluxed at120° C. for 3 hours and was then concentrated. The crude was dissolvedin ethanol (5 ml), cooled to 0° C. and treated with sodium borohydride(0.6 g, 15.7 mmol). After warming to room temperature, the mixture wasrefluxed for 3 hours. The mixture was concentrated and the residue wassuspended between water and diethyl ether. The diethyl ether layer wasseparated and concentrated to dryness. The crude material was purifiedby silica gel chromatography, eluting with 5% methanol/chloroform toafford the desired product as a pale yellow solid (0.3 g, 27%): mp65-67° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.91 (bs, 1H), 8.46 (d, J=4.5 Hz,1H), 7.99 (d, J=8.3 Hz, 1H), 7.43 (s, 1H), 7.41 (s, 1H), 7.36 (dd,J=8.3, 4.7 Hz, 1H), 2.86 (d, J=12.4 Hz, 3H); ESIMS m/z 175 ([M+1]).

Example 8 Preparation of ethyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine

Method A:

To 1-pyridin-3-yl-1H-pyrazol-4-ylamine (0.5 g, 3.12 mmol) indichloromethane (5 ml) was added acetyl chloride (0.28 g, 3.75 mmol)followed by DMAP (0.57 g, 4.68 mmol) and stirred at room temperature for3 hours. The reaction mixture was concentrated and purified by silicagel column chromatography. The recovered material was dissolved intetrahydrofuran (5 ml) and lithium aluminum hydride (0.23 g, 6.25 mmol)was added and stirred at room temperature for 12 hours. The reaction wasquenched with saturated Na₂SO₄ and filtered through celite. The filtratewas collected and concentrated to dryness. The crude material waspurified by silica gel column chromatography eluting with 0-5%methanol/chloroform and resubjected to silica gel chromatography,eluting with 0-100% ethyl acetate/hexanes) to give the desired product(0.080 g, 14%): ¹H NMR (400 MHz, CDCl₃) δ 8.90 (d, J=2.7 Hz, 1H), 8.46(dd, J=4.7, 1.3 Hz, 1H), 7.98 (ddd, J=8.3, 2.6, 1.5 Hz, 1H), 7.41 (dt,J=13.3, 6.6 Hz, 2H), 7.36 (ddd, J=8.3, 4.7, 0.7 Hz, 1H), 3.10 (q, J=7.1Hz, 2H), 1.27 (t, 3H).

Method B:

To a solution of tert-butylethyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (3.4 g, 11.79 mmol) indichloromethane (4.54 ml) was added trifluoroacetic acid (9 ml), and thereaction mixture was stirred for 1 hour at room temperature. Toluene wasadded and the reaction was concentrated to near dryness. The reactionwas poured into a separatory funnel and carefully quenched withsaturated aqueous NaHCO₃ and extracted with dichloroethane. The organiclayer was dried (MgSO₄), filtered and concentrated to dryness. The crudeproduct was purified by silica gel chromatography (0-10%MeOH/dichloromethane) to give the desired product as a pale yellow oil(2.10 g, 95%): ¹H NMR (400 MHz, CDCl₃) δ 8.90 (dd, J=1.8, 0.8 Hz, 1H),8.51-8.39 (m, 1H), 7.97 (ddt, J=8.3, 2.7, 1.3 Hz, 1H), 7.41 (d, J=0.8Hz, 2H), 7.38-7.30 (m, 1H), 3.21-2.93 (m, 2H), 1.34-1.19 (m, 3H).

3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared asdescribed in Example 8, Method B: ¹H NMR (400 MHz, CDCl₃) δ 8.87 (d,J=2.5 Hz, 1H), 8.47 (dd, J=4.7, 1.2 Hz, 1H), 7.96 (ddd, J=8.4, 2.6, 1.4Hz, 1H), 7.38-7.32 (m, 2H), 3.11 (q, J=7.1 Hz, 2H), 2.97 (bs, 1H), 1.31(t, J=7.1 Hz, 3H).

3-chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as inExample 8, Method B: mp 108-118 C; ¹H NMR (400 MHz, CDCl₃) δ 8.88 (d,J=2.4 Hz, 1H), 8.48 (dd, J=4.7, 1.4 Hz, 1H), 7.96 (ddd, J=8.3, 2.7, 1.4Hz, 1H), 7.41-7.29 (m, 2H), 2.87 (s, 3H); EIMS m/z 208.

N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as inExample 8, Method B: ¹H NMR (400 MHz, CDCl₃) δ 9.03-8.73 (m, 1H), 8.41(dd, J=4.7, 1.4 Hz, 1H), 7.95 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.42-7.27(m, 2H), 2.85 (s, 4H), 2.25 (s, 3H); EIMS m/z 189

3-chloro-N-(cylopropylmethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine wasprepared as in Example 8, Method B: ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d,J=2.5 Hz, 1H), 8.47 (dd, J=4.7, 1.4 Hz, 1H), 8.03-7.89 (m, 1H),7.40-7.29 (m, 2H), 3.21 (s, 1H), 2.91 (d, J=4.4 Hz, 2H), 1.18-1.02 (m,1H), 0.65-0.45 (m, 2H), 0.41-0.12 (m, 2H).

3-chloro-N-propyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared as inExample 8, Method B: ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.6 Hz, 1H),8.47 (dd, J=4.7, 1.4 Hz, 1H), 8.01-7.89 (m, 1H), 7.42-7.27 (m, 2H),3.23-2.84 (m, 3H), 1.77-1.59 (m, 2H), 1.03 (t, J=7.4 Hz, 3H).

1-(5-Fluoropyridin-3-yl)-N,3-dimethyl-1H-pyrazol-4-amine was preparedfrom the appropriate Boc-amine as described in Example 8, Method B: mp142.0-143.5° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.26 (d, J=2.3Hz, 1H), 7.73 (dt, J=10.0, 2.4 Hz, 1H), 7.27 (s, 1H), 2.92-2.81 (m, 4H),2.24 (s, 3H); ESIMS m/z 207 ([M+H]⁺).

N-ethyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: mp 85.0-86.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.66 (s, 1H), 8.25(d, J=2.5 Hz, 1H), 7.72 (dt, J=10.0, 2.3 Hz, 1H), 7.27 (s, 1H), 3.07 (q,J=7.1 Hz, 2H), 2.71 (s, 1H), 2.25 (s, 3H), 1.30 (t, J=7.1 Hz, 3H); ESIMSm/z 221 ([M+H]⁺).

3-Methyl-N-propyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared fromthe appropriate Boc-amine as described in Example 8, Method B: mp65.0-67.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.4 Hz, 1H), 8.40(dd, J=4.7, 1.4 Hz, 1H), 7.94 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.35-7.28(m, 2H), 3.00 (t, J=7.1 Hz, 2H), 2.26 (s, 3H), 1.76-1.58 (m, 2H), 1.03(t, J=7.4 Hz, 3H); ESIMS m/z 217 ([M+H]⁺).

N-(cyclopropylmethyl)-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: mp 73.0-75.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.4 Hz,1H), 8.40 (dd, J=4.7, 1.3 Hz, 1H), 7.94 (ddd, J=8.3, 2.6, 1.5 Hz, 1H),7.35-7.28 (m, 2H), 2.87 (d, J=6.9 Hz, 2H), 2.75 (s, 1H), 2.28 (s, 3H),1.22-1.05 (m, 1H), 0.63-0.56 (m, 2H), 0.26 (q, J=4.7 Hz, 2H); ESIMS m/z229 ([M+H]⁺).

N-isopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was preparedfrom the appropriate Boc-amine as described in Example 8, Method B: IR(thin film) 3303 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.3 Hz, 1H),8.41 (dd, J=4.7, 1.4 Hz, 1H), 7.94 (ddd, J=8.3, 2.7, 1.5 Hz, 1H),7.36-7.28 (m, 2H), 3.30 (hept, J=6.3 Hz, 1H), 2.25 (s, 3H), 1.24 (d,J=6.3 Hz, 6H); EIMS m/z 216.

5-Ethoxy-1-(5-fluoropyridin-3-yl)-N,3-dimethyl-1H-pyrazol-4-amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: IR (thin film) 3340 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.91 (s,1H), 8.31 (d, J=2.5 Hz, 1H), 7.88-7.80 (m, 1H), 4.24 (q, J=7.1 Hz, 2H),2.79 (s, 3H), 2.24 (s, 3H), 1.36 (t, J=7.1 Hz, 3H); EIMS m/z 250.

5-Bromo-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared fromthe appropriate Boc-amine as described in Example 8, Method B: mp77.0-79.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.90 (d, J=2.0 Hz, 1H), 8.63(d, J=3.9 Hz, 1H), 7.93 (ddd, J=8.2, 2.4, 1.5 Hz, 1H), 7.51 (s, 1H),7.43 (dd, J=8.2, 4.8 Hz, 1H), 4.49 (s, 1H), 2.91 (s, 3H); ESIMS m/z 255([M+2]⁺).

5-Fluoro-N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was preparedfrom the appropriate Boc-amine as described in Example 8, Method B: ¹HNMR (400 MHz, CDCl₃) δ 8.91 (t, J=2.1 Hz, 1H), 8.50 (dd, J=4.8, 1.5 Hz,1H), 7.93 (ddt, J=8.3, 2.8, 1.5 Hz, 1H), 7.37 (ddd, J=8.3, 4.8, 0.7 Hz,1H), 2.86 (d, J=1.6 Hz, 3H), 2.43 (s, 2H), 2.24 (s, 3H); EIMS m/z 206.

5-Bromo-N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was preparedfrom the appropriate Boc-amine as described in Example 8, Method B: ¹HNMR (400 MHz, CDCl₃) δ 8.86 (dd, J=2.5, 0.5 Hz, 1H), 8.59 (dd, J=4.8,1.5 Hz, 1H), 7.88 (ddd, J=8.2, 2.6, 1.5 Hz, 1H), 7.40 (ddd, J=8.2, 4.8,0.7 Hz, 1H), 2.85 (s, 3H), 2.69 (s, 1H), 2.35 (s, 3H); ESIMS m/z 268([M+H]⁺).

5-Chloro-N,3-dimethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was preparedfrom the appropriate Boc-amine as described in Example 8, Method B: ¹HNMR (400 MHz, CDCl₃) δ 8.87 (d, J=2.3 Hz, 1H), 8.59 (dd, J=4.8, 1.3 Hz,1H), 7.90 (ddd, J=8.2, 2.6, 1.5 Hz, 1H), 7.40 (ddd, J=8.2, 4.8, 0.6 Hz,1H), 2.87 (s, 3H), 2.45-2.19 (m, 4H); EIMS m/z 223.

3-Chloro-1-(5-fluoropyridin-3-yl)-N-methyl-1H-pyrazol-4-amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: mp 117.5-119.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.68 (d, J=1.1Hz, 1H), 8.33 (d, J=2.5 Hz, 1H), 7.75 (dt, J=9.6, 2.4 Hz, 1H), 7.31 (s,1H), 3.14 (s, 1H), 2.87 (s, 3H); ESIMS m/z 227 ([M]⁺).

3-Chloro-N-ethyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: ¹H NMR (400 MHz, CDCl₃) δ 8.70-8.63 (m, 1H), 8.32 (d, J=2.4Hz, 1H), 7.74 (dt, J=9.7, 2.4 Hz, 1H), 7.31 (s, 1H), 3.11 (q, J=7.2 Hz,2H), 1.31 (t, J=7.1 Hz, 3H).

1-(5-Fluoropyridin-3-yl)-N-methyl-3-vinyl-1H-pyrazol-4-amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: 105.0-107.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.72 (s, 1H), 8.31(d, J=2.5 Hz, 1H), 7.81 (dt, J=9.8, 2.4 Hz, 1H), 7.33 (s, 1H), 6.75 (dd,J=18.0, 11.6 Hz, 1H), 5.83 (dd, J=18.0, 1.1 Hz, 1H), 5.46 (dd, J=11.6,1.1 Hz, 1H), 2.86 (s, 3H); ESIMS m/z 219 ([M+H]⁺).

3-Cyclopropyl-1-(5-fluoropyridin-3-yl)-N-methyl-1H-pyrazol-4-amine wasprepared from the appropriate Boc-amine as described in Example 8,Method B: mp 118.0-119.5° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.66-8.58 (m,1H), 8.23 (d, J=2.5 Hz, 1H), 7.75-7.68 (m, 1H), 7.25 (s, 1H), 3.09 (s,1H), 2.86 (s, 3H), 1.78-1.63 (m, 1H), 0.99-0.90 (m, 4H); ESIMS m/z 233([M+H]⁺).

3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from theappropriate Boc-amine as described in Example 8, Method B: mp137.9-139.9; ¹H NMR (400 MHz, CDCl₃) δ 8.84 (d, J=2.4 Hz, 1H), 8.50 (dd,J=4.7, 1.4 Hz, 1H), 7.95 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.52 (s, 1H),7.37 (ddd, J=8.4, 4.7, 0.7 Hz, 1H), 3.18 (s, 2H); ESIMS m/z 196([M+H]⁺).

2-((3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)amino)acetonitrile wasprepared from tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(cyanomethyl)carbamate as inExample 8, Method B: mp 141-143° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.91 (d,J=2.7 Hz, 1H), 8.54 (dd, J=5.1, 1.8 Hz, 1H), 7.97 (m, 1H), 7.62 (s, 1H),7.38 (dd, J=12.0, 7.5 Hz, 1H), 4.97 (d, J=6.9 Hz, 2H), 3.52 (m, 1H);EIMS m/z 235 ([M+H]⁺).

N-3-dimethyl-1-(pyrimidin-5-yl)-1H-pyrazol-4-amine was prepared as inExample 8, Method B: mp 139-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.02 (s,2H), 9.00 (s, 1H), 7.30 (s, 1H), 2.87 (d, J=11.5 Hz, 3H), 2.27 (s, 3H);ESIMS m/z 190 ([M+H]).

3-chloro-N-methyl-1-(pyrimidin-5-yl)₁₋₁H-pyrazol-4-amine was prepared asin Example 8, Method B: mp 111-114° C.; ¹H NMR (400 MHz, CDCl₃) δ9.09-9.04 (m, 1H), 9.02 (s, 2H), 7.30 (s, 1H), 3.14 (bs, 1H), 2.88 (s,3H); ESIMS m/z 196 ([M+H]).

1-(5-Fluoro-3-pyridyl)-3-methyl-N-(trideuteriomethyl)pyrazol-4-amine wasprepared from compound 380 using the procedure as described in Example8, method B: mp 146-148° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H),8.25 (d, J=2.5 Hz, 1H), 7.73 (dt, J=10.0, 2.3 Hz, 1H), 7.27 (s, 1H),2.87 (s, 1H), 2.24 (s, 3H); ESIMS m/z 210 ([M+H]⁺); IR (Thin film) 1599cm⁻¹.

3-Chloro-1-(3-pyridyl)-N-(trideuteriomethyl)pyrazol-4-amine was preparedfrom compound 381 using the procedure as described in Example 8, methodB: mp 104-106° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.87 (d, J=1.9 Hz, 1H),8.47 (d, J=4.7 Hz, 1H), 8.00-7.90 (m, 1H), 7.40-7.30 (m, 2H), 3.10 (s,1H); ESIMS m/z 212 ([M+H]⁺); IR (Thin film) 1579 cm⁻¹.

3-Chloro-N-(cyclopropylmethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine wasprepared from compound 361 using the procedure as described in Example8, method B: mp 82-83° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.5 Hz,1H), 8.47 (dd, J=4.7, 1.3 Hz, 1H), 7.95 (ddd, J=8.4, 2.7, 1.5 Hz, 1H),7.38-7.32 (m, 2H), 3.22 (s, 1H), 2.90 (d, J=6.9 Hz, 2H), 1.23-1.06 (m,1H), 0.65-0.53 (m, 2H), 0.31-0.19 (m, 2H); ESIMS m/z 249 ([M+H]⁺);

3-Chloro-N-propyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared fromcompound 360 using the procedure as described in Example 8, method B: mp92-94° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.6 Hz, 1H), 8.47 (dd,J=4.7, 1.4 Hz, 1H), 7.95 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.35 (ddd,J=8.4, 4.7, 0.6 Hz, 1H), 7.33 (s, 1H), 3.22-2.94 (m, 3H), 1.75-1.52 (m,2H), 1.02 (t, J=7.4 Hz, 3H); ESIMS m/z 237 ([M+H]⁺).

Example 9 Preparation ofisopropyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine

1-pyridin-3-yl-1H-pyrazol-4-ylamine (0.6 g, 3.7 mmol) was dissolved inisopropyl acetate (8.5 ml). To the mixture, acetone (0.261 g, 4.5 mmol),trifluoroacetic acid (0.855 g, 7.5 mmol) and sodiumtriacetoxyborohydride (0.945 g, 4.5 mmol) were added. The reaction wasstirred under nitrogen at room temperature for 4.5 hours and thenquenched with 10% sodium hydroxide solution until the pH reached ˜9. Thelayers were separated, and the aqueous phase was extracted with ethylacetate. The organic extracts were combined, dried over sodium sulfateand concentrated to dryness. The crude material was purified by silicagel chromatography (gradient elution of 5% methanol/dichloromethane) togive the title compound as an off white solid (0.35 g, 46%): mp 105-107°C.; ¹H NMR (300 MHz, CDCl₃) δ 8.82 (d, J=2.2 Hz, 1H), 8.63 (dd, J=4.8,1.5 Hz, 1H), 8.13 (d, J=1.8 Hz, 1H), 8.03 (d, J=2.7 Hz, 1H), 7.94-7.77(m, 1H), 7.38 (dt, J=15.2, 7.6 Hz, 1H), 6.99 (t, 1H), 3.72 (m, 1H), 1.30(t, J=10.0 Hz, 6H). ESIMS 214 m/z (M+1).

Example 10 Preparation of propyl-(1-pyridin-3-yl-1H-pyrazol-4-yl-amine

To 1-pyridin-3-yl-1H-pyrazol-4-ylamine (0.5 g, 3.12 mmol) indichloromethane (5 ml) was added propionaldehyde (0.18 g, 3.12 mmol) andsodium triacetoxy borohydride (0.99 g, 4.68 mmol) and stirred at roomtemperature for 16 hours. The reaction was taken up in dichloromethaneand was washed with water and brine. The organic layer was dried(MgSO₄), filtered and concentrated to dryness. The crude material waspurified by silica gel chromatography eluting with 0-5%MeOH/Dichloromethane and resubjected in 0-100% ethylacetate/hexanes) togive the title compound as a dark oil (0.05 g, 7%): ¹H NMR (300 MHz,CDCl₃) δ 8.92 (d, J=2.6 Hz, 1H), 8.48 (dd, J=4.7, 1.4 Hz, 1H), 8.00(ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.47-7.40 (m, 2H), 7.37 (dd, J=8.3, 4.7Hz, 1H), 3.04 (t, J=7.1 Hz, 3H), 1.92-1.46 (m, 2H), 1.03 (t, J=7.4 Hz,3H).

Example 11 Preparation ofN-methyl-N-(1-pyridin-3-yl-1H-pyrazol-4-yl)-isobutyramide (Compound 42)

A solution of isobutyryl chloride (0.138 g, 1.3 mmol) in dichloroethane(1 mL) was pipetted at a dropwise rate into an ice-cold suspension ofmethyl-(1-pyridin-3-yl-1H-pyrazol-4-yl)-amine (0.15 g, 0.86 mmol) indichloroethane (5 mL), stirred for 10 minutes and then treated at adropwise rate with a solution of 4-N,N-dimethylaminopyridine (0.11 g,0.9 mmol) in dichloroethane (1.5 mL). The cooling bath was removed after30 minutes, stirred under nitrogen at room temperature for 14 hours,diluted with dichloroethane (40 mL), washed with water (30 mL), brine(10 mL), dried over MgSO₄ and purified by reversed phase columnchromatography to give a yellowish gum (0.114 g, 54%) ¹H NMR (300 MHz,CDCl₃) δ 9.01-8.93 (m, 1H), 8.67 (s, 0.4H), 8.61 (d, J=4.2 Hz, 0.6H),8.54 (d, 0.4H), 8.08-8.02 (m, 1H), 7.96 (s, 0.6H), 7.80 (s, 0.4H), 7.70(s, 0.6H), 7.47-7.37 (m, 1H), 3.49 (s, 1.2H), 3.26 (s, 2.8H), 3.06-2.98(m, 0.4H), 2.86-2.70 (m, 0.6H), 1.25 (d, J=6.1 Hz, 2.4H), 1.09 (d, J=6.6Hz, 3.6H). ESIMS m/z 245 ([M+1]).

Compounds 32-41, 43-52, 54-56, 59-61, 66, 73-75, 77-79, 82-85, 93-100,113, 117-129, 131-134, 139-140, 142-144, 148, 160, 163, 173-175,184-186, 197-198, 202, 208, 215-217, 252-253, 277, 282-285, 287-290,314-316, 347, 350-351, 353-355, 365-367, 370, 388, 395, 399-403, 407,409, 415-418, 444-449, 452-454, 462-463, 465, 467-469, 496-498, 506-507,512, 525-527, 569, 577, 581, 591 and 592 were made from the appropriateamines in accordance with the procedures disclosed in Example 11.

Example 12 Preparation of4,4,4-trifluoro-2-methyl-N-(1-(pyridin-3-yl)-1H-pyrazol-4-yl)butanamide(Compound 65)

To a solution of 1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.150 g, 0.93mmol) in dichloroethane (1.8 ml) was added4,4,4-trifluoro-2-methylbutanoic acid (0.14 g, 0.93 mmol) and4-N,N-dimethylaminopyridine (0.23 g, 1.87 mmol) followed by1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.36 g,1.87 mmol). The reaction stirred at room temperature overnight. Thereaction mixture was concentrated and the crude product was purified bysilica gel chromatography eluting with 0-5% MeOH/dichloromethane to givea white solid (0.15 g, 55%); mp 140-145° C.; ¹H NMR (400 MHz, CDCl₃) δ9.00 (d, J=2.4 Hz, 1H), 8.62-8.47 (m, 2H), 8.01 (ddd, J=8.3, 2.7, 1.5Hz, 1H), 7.68 (s, 1H), 7.53 (bs, 1H), 7.40 (ddd, J=8.3, 4.8, 0.6 Hz,1H), 2.92-2.61 (m, 2H), 2.32-2.05 (m, 1H), 1.38 (d, J=6.6 Hz, 3H); ESIMSm/z 300 ([M+2]).

Compounds 53, 58, 62-63, 72, 76, 80-81, 107-108, 136-138, 147, 151-159,164-168, 176-179, 187-196, 201, 203-207, 209-214, 220, 224-249, 251,259-275, 286, 292-296, 303-313, 323-326, 341-344, 356-359, 371, 378-379,382, 384, 419-426, 439-443, 455, 458-461, 464, 466, 476, 486, 490-493,505, 508, 517, 528-529, 536-537, 539-541, 544-545, 549-554, 572-577,578, 579 and 580 were prepared from the appropriate amines in accordancewith the procedures disclosed in Example 12.

Example 13 Preparation of tert-butyl1-(pyridin-3-yl)-1H-pyrazol-4-ylcarbamate (Compound 57)

Method A:

To a solution of 1-(pyridin-3-yl)-1H-pyrazol-4-amine (3 g, 18.73 mmol)in dichloromethane (33.4 ml) was added triethylamine (3.13 ml, 7.68mmol) and BOC-anhydride (4.5 g, 20.60 mmol). The resulting solution wasstirred at room temperature overnight. The reaction mixture waspartitioned between ethyl acetate and water. The organic portion wasdried (MgSO₄), filtered and concentrated to dryness. The crude productwas purified by silica gel chromatography eluting with 0-100% ethylacetate/hexanes to yield a white solid (2.0 g, 41%); mp 108-112° C.; ¹HNMR (400 MHz, CDCl₃) δ 9.02 (d, J=2.2 Hz, 1H), 8.51 (t, J=8.7 Hz, 1H),8.37 (s, 1H), 8.30 (s, 1H), 7.98 (ddd, J=8.3, 2.4, 1.3 Hz, 1H), 7.68 (s,1H), 7.36 (dd, J=8.2, 4.8 Hz, 1H), 1.52 (s, 9H); ESIMS m/z 261 ([M+1]).

Compounds 64 and 130 were prepared in accordance with the proceduresdisclosed in Example 13, Method A.

Method B:

To a solution of 1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.1 g, 0.624 mmol)and di-tert-butyl dicarbonate (0.161 ml, 0.693 mmol) in tetrahydrofuran(1.890 ml) and water (0.568 ml) was added dropwise saturated aqueoussodium bicarbonate (0.572 ml, 0.687 mmol). The reaction was stirred atroom temperature overnight. The reaction was diluted with water andextracted with ethyl acetate. The combined organic phases wereconcentrate to give tert-butyl 1-(pyridin-3-yl)-1H-pyrazol-4-ylcarbamate(135 mg, 0.519 mmol, 83%), for which the analytical data was consistentwith that reported in Example 13, Method A.

Compounds 150, 172, 223, and 317 were prepared in accordance with theprocedures disclosed in Example 13, Method B. Compound 172 and 317 wasalso prepared in accordance with the procedures disclosed in Example 17.These compounds, as well as, certain other compounds, were made byalternative methods further illustrating certain embodiments.

Example 14 Preparation of tert-butylmethyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 67)

To a solution of tert-butyl 1-(pyridin-3-yl)-1H-pyrazol-4-ylcarbamate(1.6 g, 6.15 mmol) in DMF (30.7 ml) at 0° C. was added sodium hydride(0.34 g, 8.61 mmol, 60% dispersion in mineral oil) in one portion andthe suspension was stirred for 30 minutes. The ice bath was removed andstirred for an additional 30 minutes. Iodomethane (0.46 ml, 7.38 mmol)was added in one portion and stirred overnight at room temperature.Water and ethyl acetate were added and the resulting biphasic mixturewas separated. The aqueous layer was extracted one time with ethylacetate. The combined organic extracts were washed with brine, dried(MgSO₄), filtered and concentrated to dryness. The crude product waspurified by silica gel chromatography eluting with 0-35% ethylacetate/hexanes to yield a light yellow semi-solid (0.85 g, 50%): IR(KBr) 1703 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.98 (s, 1H), 8.52 (d, J=3.8Hz, 1H), 8.32 (s, 0.5H), 8.13-7.97 (m, 1H), 7.84 (s, 0.5H), 7.74 (s,1H), 7.39 (dd, J=8.0, 4.8 Hz, 1H), 3.30 (s, 3H), 1.56 (s, 9H); ESIMS m/z275 ([M+H]).

Compounds 68, 86-92, 105-106, 114-116, 141, 149, 161-162, 199-200, 254,258, 291, 332, 352, 360-361, 380-381, 414, 430-431, 450, 457, 474-475,485, 488, 510-511, 515, 523, and 590 were prepared from the appropriateamides in accordance with the procedures disclosed in Example 14.

Tert-butyl methyl(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamatewas prepared as in Example 14: ¹H NMR (400 MHz, CDCl₃) δ 8.91 (d, J=2.5Hz, 1H), 8.51 (dd, J=4.7, 1.3 Hz, 1H), 8.00 (ddd, J=8.3, 2.4, 1.4 Hz,1H), 7.83 (s, 1H), 7.38 (dd, J=8.3, 4.7 Hz, 1H), 3.20 (s, 3H), 2.22 (s,3H), 1.60-1.30 (m, 9H).

Example 15 Preparation ofN-ethyl-N-(1-methyl-3-(pyridin-3-yl)-1H-pyrazol-5-yl)isobutyramide(Compound 23)

To a solution ofN-(1-methyl-3-(pyridine-3-yl)-1H-pyrazol-5-yl)isobutyramide (0.08 g,0.33 mmol) in DMF (0.66 ml) at 0° C. was added sodium hydride (0.016 g,0.39 mmol, 60% dispersion in mineral oil) in one portion and thesuspension was stirred for 30 minutes. The ice bath was removed andstirred for an additional 30 minutes. Iodoethane (0.06 g, 0.39 mmol) wasadded in one portion and stirred overnight at room temperature. Waterand ethyl acetate were added and the resulting biphasic mixture wasseparated. The aqueous layer was extracted one time with ethyl acetate.The combined organic extracts were washed with brine, dried (MgSO₄),filtered and concentrated to dryness. The crude product was purified bysilica gel chromatography to give the title compound as a clear oil(27.5 mg, 30%): ¹H NMR (300 MHz, CDCl₃) δ 9.00 (bs, 1H), 8.57 (s, 1H),8.09 (dd, J=7.9 Hz, 1H), 7.34 (dd, 1H), 6.48 (s, 1H), 4.00 (m, 1H), 3.76(s, 3H), 3.36 (m, 1H), 2.33 (m, 1H), 1.17 (t, J=7.1 Hz, 3H), 1.08 (t,J=6.7 Hz, 6H); ESIMS m/z 273 (M+H).

Compound 22 was prepared in accordance with the procedures disclosed inExample 15.

Example 16 Preparation of 5-bromo-1H-pyrazol-4-amine, HBr

A mixture of 4-nitro-1H-pyrazole (10 g, 88 mmol) and 5% palladium onAl₂O₃ (1 g) in a mixture of ethanol (150 mL) and 50% aqueous HBr (50 mL)was shaken in a Par apparatus under hydrogen (10 psi) for 36 h. Themixture was filtered and the catalyst washed with ethanol. The filtratewas concentrated in vacuo to give a white solid. This solid wassuspended in 10 mL of ethanol. After swirling the flask for 5 min, etherwas added to complete the crystallization. The solid was filtered, waswashed with ether and dried under high vacuum to afford5-bromo-1H-pyrazol-4-amine, HBr (18.1 g, 84% yield) as a white solid: mp248° C. dec; ¹H NMR (400 MHz, DMSO-d₆) δ 11.47 (s, 1H), 10.00 (s, 1H),7.79 (s, 1H).

Example 17 Preparation of tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 172)Example 17 Step 1: Preparation of 3-chloro-1H-pyrazol-4-aminehydrochloride

Into a 2 L three-necked round bottom flask affixed with an overheadstirrer, a temperature probe, an addition funnel, and a nitrogen inletwere added ethanol (600 mL) and 4-nitro-1H-pyrazole (50.6 g, 447 mmol).To this solution was added, in one portion, conc. HCl (368 mL) (note:rapid exotherm from 15° C. to 39° C.) and the resulting mixture waspurged with nitrogen for 5 minutes. Palladium on alumina (5% w/w) (2.6g, Alfa, black solid) was added to the mixture and stirred at roomtemperature while triethylsilane (208 g, 1789 mmol) was added drop-wiseover 4 h. The reaction, which started to slowly exotherm from 35° C. to55° C. over 2.0 h, was stirred for a total of 16 h and vacuum filteredthrough a plug of Celite® to give a biphasic mixture. The mixture wastransferred to a separatory funnel, the bottom aqueous layer wascollected and rotary evaporated (60° C., 50 mmHg) to dryness with theaid of acetonitrile (3×350 mL). The resulting yellow solid was suspendedin acetonitrile (150 mL) and allowed to stand for 2 h at roomtemperature followed by 1 h at 0° C. in the refrigerator. The solidswere filtered and washed with acetonitrile (100 mL) to afford the titledcompound 3-chloro-1H-pyrazol-4-amine hydrochloride (84 g, 97% yield, 80%purity) as a white solid: mp 190-193° C.; ¹H NMR (400 MHz, DMSO-d₆) δ10.46-10.24 (bs, 2H), 8.03 (s, 0.54H), 7.75 (s, 0.46H), 5.95 (bs, 1H));¹³C-NMR (101 MHz, DMSO) δ 128.24, 125.97, 116.71.

Example 17 Step 2: Preparation of tert-butyl(3-chloro-1H-pyrazol-4-yl)carbamate

Into a 2 L round bottom flask was added 3-chloro-1H-pyrazol-4-aminehydrochloride (100 g, 649 mmol) and THF (500 mL). To this mixture wereadded di-tert-butyldicarbonate (156 g, 714 mmol) followed by sodiumbicarbonate (120 g, 1429 mmol) and water (50.0 ml). The mixture wasstirred for 16 h, diluted with water (500 mL) and ethyl acetate (500 mL)and transferred to a separatory funnel. This gave three layers; bottom—awhite gelatinous precipitate, middle—light yellow aqueous, top—auburnorganic. The phases were separated collecting the white gelatinousprecipitate and the aqueous layer together. The aqueous was extractedwith ethyl acetate (2×200 mL) and the ethyl acetate extracts werecombined, washed with brine (200 mL), dried over anhydrous sodiumsulfate, filtered and rotary evaporated to give an auburn thick oil (160g.). The thick oil was suspended in hexane (1000 mL) and stirred at 55°C. for 2 h. This gave a light brown suspension. The mixture was cooledto 0° C. and the solid collected by vacuum filtration and rinsed withhexane (2×10 mL). The sample was air dried to constant mass to afford(3-chloro-1H-pyrazol-4-yl)carbamate (102.97 g, 72% yield, 80% purity) asa light brown solid: mp 137-138° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.69 (s,1H), 7.91 (s, 1H), 1.52 (s, 9H).

Example 17 Step 3: Preparation of tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 172)

To a dry 2 L round bottom flask equipped with mechanical stirrer,nitrogen inlet, thermometer, and reflux condenser was charged the3-iodopyridine (113.0 g, 551 mmol), (3-chloro-1H-pyrazol-4-yl)-carbamate(100 g, 459 mmol), potassium phosphate (powdered in a mortar and pestle)(195 g, 919 mmol), and copper chloride (3.09, 22.97 mmol). Acetonitrile(1 L) followed by N¹,N²-dimethylethane-1,2-diamine were added and themixture was heated to 81° C. for 4 hours. The mixture was cooled to roomtemperature and filtered through a bed of Celite®. The filtrate wastransferred to a 4 L Erlenmeyer flask equipped with mechanical stirrerand diluted with water until the total volume was about 4 L. The mixturewas stirred for 30 minutes at room temperature and the resulting solidwas collected by vacuum filtration. The solid was washed with water andwashed with water and oven dried for several days in vacuo at 40° C. toa constant weight to give tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (117.8 g, 87%yield, 80% purity) as a tan solid: mp 140-143° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.96 (s, 1H), 8.53 (dd, J=4.7, 1.2 Hz, 1H), 8.36 (s, 1H), 7.98(ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.38 (dd, J=8.3, 4.8 Hz, 1H), 6.37 (s,1H), 1.54 (s, 9H); ESIMS (m/z) 338 ([M-t-Bu]⁺), 220 ([M-O-t-Bu]⁻).

Compound 172 was also prepared in accordance with the proceduresdisclosed in Example 13. Compound 317 was prepared in accordance withthe procedures disclosed in Example 17 from tert-butyl(3-bromo-1H-pyrazol-4-yl)carbamate and also in accordance with theprocedures disclosed in Example 13.

Example 18 Preparation of 3-(3-methyl-1H-pyrazol-1-yl)pyridine and3-(5-methyl-1H-pyrazol-1-yl)pyridine

To a solution of 3-methyl-1H-pyrazole (10.99 g, 134 mmol) inN,N-dimethylformamide (100 ml) at 0° C. was added sodium hydride (3.71g, 154 mmol, 60% dispersion). The reaction was stirred at 0° C. for 2hours. 3-Fluoropyridine (10.0 g, 103 mmol) was added, and the reactionwas stirred at 100° C. overnight. The reaction was cooled to roomtemperature and water was added slowly. The mixture was extracted withdichloromethane and the combined organic phases were washed with brine,concentrated and chromatographed (0-100% ethyl acetate/hexanes) toafford 3-(3-methyl-1H-pyrazol-1-yl)pyridine (8.4 g, 52.77 mmol, 51.2%)and 3-(5-methyl-1H-pyrazol-1-yl)pyridine (1.0 g, 6%). Analytical data ofboth products is consistent with that reported under Example 6, Step 1.

3-(3-Bromo-1H-pyrazol-1-yl)pyridine was prepared from 3-fluoropyridineand 3-bromopyrazole, which was made as in WO2008130021, as describedExample 18: mp 89.5-92.5° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.94 (d, J=2.4Hz, 1H), 8.62-8.49 (m, 1H), 8.03 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.87 (d,J=2.5 Hz, 1H), 7.42 (dd, J=8.2, 4.7 Hz, 1H), 6.54 (d, J=2.5 Hz, 1H);ESIMS m/z 224 ([M]⁺).

Example 19 Preparation of3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine

To a stirred solution of 5-chloro-1H-pyrazol-4-amine, HCl (2 g, 12.99mmol) and cesium carbonate (8.89 g, 27.3 mmol) in DMF (13 mL) was added3,5-difluoropyridine (1.794 g, 15.58 mmol) and the mixture heated at 70°C. for 12 h. The mixture was cooled to room temperature and filtered.The solids were washed with copious amount of ethyl acetate. Thefiltrates was washed with brine, dried over anhydrous MgSO₄ andconcentrated in vacuo to give a brown solid. This solid was dissolved inethyl acetate and the resulting solution was saturated with hexanes toprecipitate 3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine (2.31g, 10.32 mmol, 79% yield) as a brown solid: ¹H NMR (400 MHz, DMSO-d₆) δ8.89-8.82 (m, 1H), 8.45 (d, J=2.5 Hz, 1H), 8.07 (d, J=10.4 Hz, 1H), 7.94(s, 1H), 4.51 (s, 2H); EIMS (m/z) 213 ([M+1]+).

3-Bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine was prepared fromthe corresponding pyrazole as described in Example 19: mp 164-165° C.;¹H NMR (400 MHz, CDCl₃) δ 8.65 (d, J=1.7 Hz, 1H), 8.36 (d, J=2.5 Hz,1H), 7.76 (dd, J=5.9, 3.6 Hz, 1H), 7.48 (s, 1H), 3.22 (s, 2H). ¹³C NMR(101 MHz, CDCl₃) δ 160.87, 158.30, 135.36, 135.13, 134.39, 134.35,131.16, 123.31, 114.02, 112.77, 112.54; EIMS (m/z) 258 ([M+1]+).

Example 20 Preparation of1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine

To a solution of 3-fluoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine(3.133 g, 14.10 mmol) in ethanol (28.2 ml) was added ethyl acetate untilall of the starting material went into solution. The solution wasdegassed and 10% palladium on carbon (0.750 g, 0.705 mmol) was added andthe reaction was stirred in a parr hydrogenator at 40 psi for 3 hours.The solution was filtered through celite with ethyl acetate andconcentrated to give1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine (2.000 g, 10.41mmol, 73.8%) as a brown solid: mp 136.0-138.0° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.67-8.59 (m, 1H), 8.27 (d, J=2.5 Hz, 1H), 7.73 (dt, J=9.9, 2.3Hz, 1H), 7.45 (s, 1H), 3.01 (s, 2H), 2.28 (s, 3H); EIMS m/z 192.

1-(Pyridin-3-yl)-3-(trifluoromethyl)-1H-pyrazol-4-amine was preparedfrom the appropriate nitropyrazole as described in Example 20: mp112.5-115.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.89 (d, J=2.4 Hz, 1H), 8.57(dd, J=4.7, 1.4 Hz, 1H), 8.03 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.56 (d,J=0.7 Hz, 1H), 7.41 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 3.47-3.31 (m, 2H);EIMS m/z 228.

Example 21 Preparation of 3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine

To 3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine (0.95 g, 4.23 mmol) inacetic acid (8.46 mL), ethanol (8.46 mL) and water (4.23 mL) was addediron powder (1.18 g, 21.15 mmol) and the reaction was stirred at roomtemperature for 30 minutes. To this was added carefully 2 M KOH andextracted with ethyl acetate. The ethyl acetate layers were combined,dried (MgSO₄), filtered and concentrated to dryness. The crude materialwas purified by silica gel chromatography (0-10%methanol/dichloromethane) to give the desired product as a white solid(0.66 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 8.84 (d, J=2.6 Hz, 1H), 8.49(dd, J=4.7, 1.4 Hz, 1H), 7.95 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.53 (s,1H), 7.37 (ddd, J=8.4, 4.7, 0.6 Hz, 1H), 3.17 (bs, 2H).

3-methyl-1-(2-methylpyridin-3-yl)-1H-pyrazol-4-amine was prepared asdescribed in Example 21: ¹H NMR (400 MHz, CDCl₃) δ 8.48 (dd, J=4.8, 1.6Hz, 1H), 7.62 (dd, J=8.0, 1.6 Hz, 1H), 7.23-7.18 (m, 2H), 2.91 (bs, 2H),2.55 (s, 3H), 2.28 (s, 3H); EIMS m/z 188.

3-Phenyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from theappropriate nitropyrazole as described in Example 21: IR (thin film)3324 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.94 (d, J=2.2 Hz, 1H), 8.47 (dd,J=4.7, 1.4 Hz, 1H), 8.07 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.87-7.80 (m,2H), 7.60 (s, 1H), 7.50-7.44 (m, 2H), 7.40-7.34 (m, 2H), 3.86 (s, 2H);EIMS m/z 236.

3-Chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine was prepared fromthe appropriate nitropyrazole as described in Example 21: mp149.0-151.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.65 (d, J=1.6 Hz, 1H), 8.35(d, J=2.4 Hz, 1H), 7.75 (dt, J=9.5, 2.4 Hz, 1H), 7.51 (s, 1H), 3.21 (s,2H); ESIMS m/z 213 ([M]⁺).

3-Bromo-1-(pyridin-3-yl)-1H-pyrazol-4-amine was prepared from theappropriate nitropyrazole as described in Example 21: mp 143.0-146.0°C.; ¹H NMR (400 MHz, CDCl₃) δ 8.85 (d, J=2.4 Hz, 1H), 8.50 (dd, J=4.7,1.4 Hz, 1H), 7.96 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.49 (s, 1H), 7.37(ddd, J=8.4, 4.7, 0.7 Hz, 1H), 3.21 (s, 2H); ESIMS m/z 241 ([M+2]⁺).

Example 22 Preparation of tert-butyl(5-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 281)

To a solution of (E)-tert-butyl1-(dimethylamino)-3-oxobut-1-en-2-ylcarbamate (0.59 g, 2.58 mmol) inethanol (2.5 mL) was added 3-hydrazinylpyridine, 2HCl (0.470 g, 2.58mmol). The reaction mixture was stirred at ambient temperature for 16hours. The reaction mixture was concentrated and purified using silicagel chromatography (0-100% ethyl acetate/hexanes) to yield the titlecompound as an orange foam (0.235 g, 30%): IR (thin film) 3268, 2978 and1698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.75 (dd, J=2.5, 0.5 Hz, 1H), 8.62(dd, J=4.8, 1.5 Hz, 1H), 7.82 (ddd, J=8.2, 2.6, 1.5 Hz, 1H), 7.78 (s,1H), 7.43 (ddd, J=8.1, 4.8, 0.6 Hz, 1H), 6.04 (s, 1H), 2.29 (s, 3H),1.52 (s, 9H); ESIMS m/z 275 ([M+H]⁺), 273 ([M−H]⁻).

Example 23 Preparation of tert-butyl1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (CompoundIII) and tert-butyl5-ethoxy-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate(Compound 112)

To a solution of 3-fluoro-5-(3-methyl-4-nitro-1H-pyrazol-1-yl)pyridine(3.133 g, 14.10 mmol) in ethanol (28.2 ml) was added ethyl acetate untilall of the starting material went into solution. The solution wasdegassed and 10% palladium on carbon (0.750 g, 0.705 mmol) was added andthe reaction was stirred in a parr hydrogenator at 40 psi for 3 hours.The solution was filtered through celite with ethyl acetate and thesolvent was removed under reduced pressure. The residue was dissolved intetrahydrofuran (32.0 ml) and water (9.61 ml). Di-tert-butyl dicarbonate(2.52 g, 11.55 mmol) was added followed by saturated aqueous sodiumbicarbonate (9.54 ml, 11.45 mmol). The reaction was stirred at roomtemperature overnight, diluted with water and extracted with ethylacetate. The combined organic phases were concentrated andchromatographed (0-100% ethyl acetate/hexanes) to give tert-butyl1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate (1.673 g,5.72 mmol, 41.0%) as a yellow solid and the tert-butyl5-ethoxy-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate(0.250 g, 0.74 mmol, 5.2%) as a brown oil:

Tert-butyl 1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate(Compound III): mp 131.5-133.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.75 (s,1H), 8.32 (d, J=2.5 Hz, 1H), 8.28 (s, 1H), 7.77 (dt, J=9.7, 2.4 Hz, 1H),6.15 (s, 1H), 2.29 (s, 3H), 1.54 (s, 9H); ESIMS m/z 293 ([M+H]⁺).

Tert-butyl5-ethoxy-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-ylcarbamate(Compound 112): IR (thin film) 1698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.88(s, 1H), 8.34 (d, J=2.5 Hz, 1H), 7.83 (d, J=9.9 Hz, 1H), 5.99 (s, 1H),4.37 (q, J=7.0 Hz, 2H), 2.17 (s, 3H), 1.50 (s, 9H), 1.37 (t, J=7.1 Hz,3H); ESIMS m/z 337 ([M+H]⁺).

Example 24 Preparation of Bis tert-t-butyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 595)

To a solution of tert-butyl (1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate(2.00 g, 7.68 mmol) in dry THF (21.95 mL) at 0° C. was added 60% sodiumhydride (0.33 g, 8.45 mmol) in one portion and stirred at thattemperature for 30 minutes. To this was then added Boc-Anhydride (1.84g, 8.45 mmol) in one portion and stirred for 5 minutes at 0° C. Thewater bath was removed and the reaction was warmed to room temperatureand stirred at additional 30 minutes. The reaction was quenched withwater and extracted with ethyl acetate. The ethyl acetate layers werecombined, dried (MgSO₄), filtered and concentrated to dryness. The crudematerial was purified by silica gel chromatography (0-100% ethylacetate/hexanes) to give the desired product as a white solid (2.0 g,72%): ¹H NMR (400 MHz, CDCl₃) δ 9.12-8.86 (m, 1H), 8.55 (dd, J=4.7, 1.4Hz, 1H), 8.04 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 8.01 (d, J=0.5 Hz, 1H),7.84-7.65 (m, 1H), 7.41 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 1.51 (s, 18H).

Example 25 Preparation of 3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine(Compound 516)

To tert-butyl (3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (2 g,6.79 mmol) in dichloromethane (6.79 ml) was added trifluoroacetic acid(6.79 ml) and the mixture was left stirring at room temperature for 2hours. Toluene (12 mL) was added and the reaction was concentrated tonear dryness. The mixture was poured into a separatory funnel containingsaturated aqueous sodium bicarbonated and was extracted withdichloromethane. The combined organic layers were concentrated to give3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.954 g, 4.90 mmol, 72.2%)as a white solid: mp 137.9-139.9° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.84 (d,J=2.4 Hz, 1H), 8.50 (dd, J=4.7, 1.4 Hz, 1H), 7.95 (ddd, J=8.3, 2.7, 1.5Hz, 1H), 7.52 (s, 1H), 7.37 (ddd, J=8.4, 4.7, 0.7 Hz, 1H), 3.18 (s, 2H);ESIMS m/z 196 ([M+H]⁺).

Example 26 Preparation ofN-allyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-aminehydrochloride

To a solution of tert-butylallyl(1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-yl)carbamate (908mg, 2.73 mmol) in dioxane (5 mL) was added HCl (1M in ether) (13.65 mL,13.65 mmol) and the mixture stirred at room temperature for 48 h. Theresulting white solid was filtered, washed with ether and dried undervacuum to giveN-allyl-1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-amine, HCl (688mg, 94% yield) as a white solid: mp 189-190° C.; ¹H NMR (400 MHz, CDCl₃)δ 8.79-8.68 (m, 1H), 8.32-8.26 (m, 1H), 8.23 (s, 1H), 7.98-7.86 (m, 1H),5.86-5.68 (m, 1H), 5.28-5.17 (m, 1H), 5.17-5.03 (m, 1H), 3.59 (d, J=6.2Hz, 2H), 2.11 (s, 3H); EIMS (m/z) 233 ([M+1]+).

N-Allyl-3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was preparedas described in Example 26 from tert-butylallyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 172-174°C.; ¹H NMR (400 MHz, CDCl₃) δ 9.20 (d, J=2.5 Hz, 1H), 8.65 (dd, J=5.3,1.1 Hz, 1H), 8.61 (ddd, J=8.6, 2.5, 1.1 Hz, 1H), 8.24 (s, 1H), 7.93 (dd,J=8.6, 5.3 Hz, 1H), 3.66 (dt, J=5.5, 1.3 Hz, 2H); EIMS (m/z) 235([M+1]+).

N-Allyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was preparedas described in Example 26 from tert-butylallyl(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl): mp 195-197° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 9.12 (d, J=2.4 Hz, 1H), 8.58 (dd, J=5.0, 1.2 Hz,1H), 8.48 (s, 1H), 8.43 (d, J=9.7 Hz, 1H), 7.77 (dd, J=8.4, 5.0 Hz, 1H),6.04-5.92 (m, 1H), 5.44 (dd, J=17.2, 1.4 Hz, 1H), 5.32 (d, J=9.4 Hz,1H), 3.81 (d, J=6.2 Hz, 2H); EIMS (m/z) 249 ([M−1]+).

3-Bromo-1-(5-fluoropyridin-3-yl)-N-methyl-1H-pyrazol-4-amine, HCl wasprepared as described in Example 26 from tert-butyl3-bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl(methyl)carbamate: mp167-168° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.93 (s, 1H), 8.50 (d, J=2.5 Hz,1H), 8.23 (s, 1H), 8.14 (dt, J=10.4, 2.3 Hz, 1H), 2.73 (s, 3H).

3-Bromo-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was preparedas described in Example 26 from tert-butyl(3-bromo-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(methyl)carbamate (160 mg,0.45 mmol) in dioxane (1 mL) was added 4M HCl: mp. 226-228° C.; ¹H NMR(400 MHz, DMSO-d₆) δ 9.26-9.06 (d, J=2.6 Hz, 1H), 8.69-8.54 (m, 1H),8.54-8.39 (d, J=8.0 Hz, 1H), 8.33-8.14 (s, 1H), 7.90-7.72 (m, 1H),2.82-2.67 (s, 3H); EIMS (m/z) 253 ([M+1]+), 255 ([M+2H]+).

3-Bromo-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl was prepared asdescribed in Example 26 from3-bromo-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl: mp 216-217°C.; ¹H NMR (400 MHz, DMSO-d₆) δ 10.66-10.05 (s, 3H), 9.28-9.20 (d, J=2.5Hz, 1H), 8.74-8.67 (m, 1H), 8.67-8.56 (m, 3H), 7.96-7.84 (m, 1H),3.21-3.14 (m, 2H), 1.29-1.22 (m, 3H); EIMS (m/z) 267 ([M+1]+).

3-Chloro-N-(2-methoxyethyl)-1-(pyridin-3-yl)-1H-pyrazol-4-amine, HCl wasprepared as described in Example 26 from tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(2-methoxyethyl)carbamate,HCl: mp 157-158° C.; ¹H NMR (400 MHz, DMSO) δ 9.22-9.14 (d, J=2.5 Hz,1H), 8.70-8.65 (s, 1H), 8.65-8.59 (m, 1H), 8.38-8.33 (m, 1H), 8.00-7.89(m, 1H), 3.59-3.50 (t, J=5.8 Hz, 2H), 3.32-3.27 (s, 3H), 3.22-3.14 (m,2H); EIMS (m/z) 253 ([M+1]+).

Example 27 Preparation of3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine hydrochloride

Into a 500 mL three-necked round bottom flask equipped with a magneticstir bar was added a solution of tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)carbamate (21 g, 65.1mmol) in 1.4-dioxane (35 mL). This pale yellow solution was placed intoan ice bath and cooled to 1° C. A solution of 4M HCl/dioxane (65 mL, 260mmol) was added in one portion. After stirring for 20 minutes, the icebath was removed and the suspension was stirred further at ambienttemperature for 16 hours. The reaction was diluted with 200 mL of ethylether and the solid was filtered and washed with ether and placed in avacuum oven at 40° C. for 18 hours. The title compound was isolated as apale yellow solid (18.2 g, 95%): ¹H NMR (400 MHz, MeOD) δ 9.52 (d, J=2.5Hz, 1H), 9.17 (s, 1H), 9.14 (ddd, J=8.7, 2.5, 1.1 Hz, 1H), 8.93 (ddd,J=5.7, 1.1, 0.6 Hz, 1H), 8.31 (ddd, J=8.7, 5.7, 0.5 Hz, 1H), 3.58 (q,J=7.3 Hz, 2H), 1.48 (t, J=7.3 Hz, 3H); ESIMS m/z 223 ([M+H]⁺).

3-Chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazole-4-amine, 2HCl wasprepared as described in Example 27: ¹H NMR (400 MHz, MeOD) δ 9.28 (d,J=2.5 Hz, 1H), 8.86 (ddd, J=8.7, 2.5, 1.2 Hz, 1H), 8.79-8.75 (m, 1H),8.62 (s, 1H), 8.19 (ddd, J=8.7, 5.6, 0.5 Hz, 1H), 3.06 (s, 3H); ¹³C NMR(101 MHz, MeOD) δ 141.42, 139.58, 137.76, 134.58, 134.11, 129.33,127.55, 122.14, 35.62); ESIMS m/z 209 ([M+H]⁺).

Example 28 Preparation of 3-(4-nitro-3-phenyl-1H-pyrazol-1-yl)pyridine

To a suspension of phenylboronic acid (0.546 g, 4.47 mmol) in toluene(6.63 ml) was added 3-(3-chloro-4-nitro-1H-pyrazol-1-yl)pyridine (0.335g, 1.492 mmol) followed by ethanol (3.31 ml) and 2 M aqueous potassiumcarbonate (1.492 ml, 2.98 mmol). The solution was degassed by applyingvacuum and then purging with nitrogen (3 times). To the reaction mixturewas added palladium tetrakis (0.086 g, 0.075 mmol) and the flask washeated at 110° C. under nitrogen for 16 hours. The aqueous layer wasremoved and the organic layer was concentrated. The crude product waspurified via silica gel chromatography (0-100% ethyl acetate/hexanes) togive 3-(4-nitro-3-phenyl-1H-pyrazol-1-yl)pyridine (499 mg, 1.874 mmol,80%) as a yellow solid: mp 144.0-146.0° C.; ¹H NMR (400 MHz, CDCl₃) δ9.09 (d, J=2.3 Hz, 1H), 8.82 (s, 1H), 8.71 (dd, J=4.8, 1.4 Hz, 1H), 8.16(ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.82-7.74 (m, 2H), 7.55-7.48 (m, 4H);EIMS m/z 266.

Example 29 Preparation of5-bromo-1-(pyridin-3-yl)-1H-pyrazol-4-ylmethyl)carbamate (Compound 110)

To tert-butyl methyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (0.200g, 0.729 mmol) in dichloroethane (3.65 ml) was added1-bromopyrrolidine-2,5-dione (0.260 g, 1.458 mmol) and the reaction wasstirred overnight at 50° C. The reaction was concentrated, diluted withdichloromethane, and washed with water and saturated aqueous sodiumthiosulfate. The organic phase was concentrated to give tert-butyl5-bromo-1-(pyridin-3-yl)-1H-pyrazol-4-yl(methyl)carbamate (256 mg, 0.725mmol, 99%) as a brown oil: IR (thin film) 1697 cm⁻¹; ¹H NMR (400 MHz,CDCl₃) δ 8.89 (s, 1H), 8.68 (d, J=4.1 Hz, 1H), 7.93 (ddd, J=8.2, 2.5,1.5 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, J=8.1, 4.8 Hz, 1H), 3.22 (s, 3H),1.44 (s, 9H); ESIMS m/z 352 ([M−H]⁻).

Example 30 Preparation of Bis tert-t-butyl(5-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 109)

To Bis tert-t-butyl (1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (1.30 g,3.61 mmol) in acetonitrile (21.22 mL) was added N-chlorosuccinimide(0.96 g, 7.21 mmol) and the reaction was stirred at 45° C. for 48 hours.The reaction was cooled to room temperature and poured into water andextracted with dichloromethane. The dichloromethane layers werecombined, poured through a phase separator to remove water andconcentrated to dryness. The crude material was purified by silica gelchromatography (0-60% ethyl acetate/hexanes) to give the desired productas a yellow solid (0.90 g, 63%): mp 109-115° C.; ¹H NMR (400 MHz, CDCl₃)δ 8.90 (d, J=2.3 Hz, 1H), 8.68 (dd, J=4.8, 1.5 Hz, 1H), 7.94 (ddd,J=8.2, 2.5, 1.5 Hz, 1H), 7.70 (s, 1H), 7.47 (dtd, J=11.0, 5.6, 5.5, 4.8Hz, 1H), 1.49 (s, 18H); ESIMS m/z 395 ([M+H]⁺).

Tert-butyl(5-chloro-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(methyl)carbamatewas prepared from the appropriate pyrazole in dichloroethane as thesolvent as described in Example 30: ESIMS m/z 324 ([M+H]⁺).

Compounds 110 (see also procedure in Example 29) and 146 were preparedfrom the appropriate pyrazoles using N-bromosuccinimide in accordancewith the procedures disclosed in Example 30.

Tert-butyl5-bromo-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl(methyl)carbamate wasprepared from the appropriate pyrazole in dichloroethane as described inExample 30: ¹H NMR (400 MHz, CDCl₃) δ 8.88 (d, J=2.3 Hz, 1H), 8.69-8.60(m, 1H), 7.96-7.86 (m, 1H), 7.48-7.39 (m, 1H), 3.18 (s, 3H), 2.26 (s,3H), 1.60-1.36 (m, 9H); ESIMS m/z 368 ([M+H]⁺).

Example 31 Preparation of bis tert-butyl(5-fluoro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 135)

To a solution of his tert-t-butyl(1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (0.075 g, 0.208 mmol) in DMF(0.416 ml) and acetonitrile (0.416 ml) was added Selecfluor® (0.184 g,0.520 mmol). The reaction was stirred at room temperature for one week.The reaction was concentrated, saturated aqueous ammonium chloride wasadded and the mixture was extracted with ethyl acetate. The combinedorganic phases were concentrated and chromatographed (0-100% ethylacetate/hexanes) to give his tert-butyl(5-fluoro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)carbamate (16 mg, 0.042 mmol,20.32%) as an off-white solid: ¹H NMR (400 MHz, CDCl₃) δ 8.97 (t, J=2.0Hz, 1H), 8.61 (dd, J=4.8, 1.4 Hz, 1H), 7.99 (ddt, J=8.3, 2.6, 1.3 Hz,1H), 7.57 (d, J=2.5 Hz, 1H), 7.44 (ddd, J=8.3, 4.8, 0.6 Hz, 1H), 1.50(s, 18H); ESIMS m/z 379 ([M+H]⁺).

Tert-butyl(5-fluoro-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(methyl)carbamatewas prepared as described in Example 31: ¹H NMR (400 MHz, CDCl₃) δ 8.94(s, 1H), 8.57 (d, J=4.2 Hz, 1H), 7.96 (d, J=7.7 Hz, 1H), 7.41 (dd,J=7.9, 4.7 Hz, 1H), 3.17 (s, 3H), 2.23 (s, 3H), 1.58-1.40 (m, 9H); ESIMSm/z 307 ([M+H]⁺).

Example 32 Preparation ofN-cyclopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine Example 32Step 1: Preparation of 3-(4-iodo-3-methyl-1H-pyrazol-1-yl)pyridine

To a mixture of 3-(3-methyl-1H-pyrazol-1-yl)pyridine (6.7 g, 42.1 mmol),iodic acid (2.96 g, 16.84 mmol), and diiodine (8.55 g, 33.7 mmol) inacetic acid (60.1 ml) was added concentrated sulfur acid (3.74 ml, 21.04mmol). The reaction mixture heated to 70° C. for 30 minutes. Thereaction mixture was poured onto ice with sodium thiosulfate and wasextracted with diethyl ether. The combined organic phases were washedwith saturated aqueous sodium bicarbonate. The organic phases were thendried with magnesium sulfate, filtered and concentrated in vacuo. Thesolid residue was dissolved in dichloromethane, applied to a 80 g silicagel column, and eluted with 0-80% acetone in hexanes to afford3-(4-iodo-3-methyl-1H-pyrazol-1-yl)pyridine (11.3 g, 35.7 mmol, 85%) asa white solid: mp 131° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.95-8.85 (m, 1H),8.52 (dd, J=4.8, 1.4 Hz, 1H), 8.00-7.94 (m, 1H), 7.91 (s, 1H), 7.38(ddd, J=8.3, 4.8, 0.7 Hz, 1H), 2.34 (s, 3H); EIMS m/z 285.

Example 32 Step 2: Preparation ofN-cyclopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine

To a solution of 3-(4-iodo-3-methyl-1H-pyrazol-1-yl)pyridine (2.0 g,7.02 mmol) in dimethylsulfoxide (7.02 ml) was added1-(5,6,7,8-tetrahydroquinolin-8-yl)ethanone (0.246 g, 1.403 mmol),cyclopropanamine (0.486 ml, 7.02 mmol), cesium carbonate (6.86 g, 21.05mmol) and copper(I) bromide (0.101 g, 0.702 mmol). The reaction mixturewas stirred at 35° C. for 2 days. The reaction mixture was diluted withwater and extracted with dichloromethane. The combined organics werewashed with brine, concentrated and chromatographed (0-100% ethylacetate/hexanes) to giveN-cyclopropyl-3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (269 mg,1.255 mmol, 17.90%) as a yellow solid: mp 104.0-107.0° C.; ¹H NMR (400MHz, CDCl₃) δ 8.89 (dd, J=2.7, 0.5 Hz, 1H), 8.41 (dd, J=4.7, 1.4 Hz,1H), 7.96 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.51 (s, 1H), 7.33 (ddd, J=8.3,4.7, 0.7 Hz, 1H), 3.42 (s, 1H), 2.53-2.42 (m, 1H), 2.22 (s, 3H),0.72-0.65 (m, 2H), 0.60-0.53 (m, 2H); ESIMS m/z 215 ([M+H]⁺).

3-Methyl-N-(3-(methylthio)propyl)-1-(pyridin-3-yl)-1H-pyrazol-4-aminewas prepared as described in Example 32: IR (thin film) 3298 cm⁻¹; ¹HNMR (400 MHz, CDCl₃) δ 8.87 (d, J=2.3 Hz, 1H), 8.40 (dd, J=4.7, 1.4 Hz,1H), 7.93 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.35 (s, 1H), 7.34-7.29 (m,1H), 3.16 (t, J=6.8 Hz, 2H), 2.89 (s, 1H), 2.64 (t, J=7.0 Hz, 2H), 2.25(s, 3H), 2.13 (s, 3H), 1.95 (p, J=6.9 Hz, 2H); ESIMS m/z 263 ([M+H]⁺).

3-Methyl-N-(2-methyl-3-(methylthio)propyl)-1-(pyridin-3-yl)-1H-pyrazol-4-aminewas prepared as described in Example 32: IR (thin film) 3325 cm⁻¹; ¹HNMR (400 MHz, CDCl₃) δ 8.86 (d, J=2.5 Hz, 1H), 8.40 (dd, J=4.7, 1.2 Hz,1H), 7.93 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.35 (s, 1H), 7.32 (ddd, J=8.3,4.7, 0.5 Hz, 1H), 3.12 (dd, J=11.5, 6.1 Hz, 1H), 2.94 (dd, J=11.9, 6.6Hz, 1H), 2.62 (dd, J=12.9, 6.9 Hz, 1H), 2.52 (dd, J=12.9, 6.2 Hz, 1H),2.26 (s, 3H), 2.14 (s, 3H), 2.12-2.02 (m, 1H), 1.11 (d, J=6.8 Hz, 3H);EIMS m/z 276.

Example 33 Preparation of tert-butyl(3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate(Compound 434) and tert-butyl(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (Compound 489)

To a suspension of 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane(1.087 g, 6.47 mmol) in toluene (13.69 ml) was added tert-butyl(3-bromo-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (1.1 g, 3.08mmol) followed by ethanol (6.84 ml) and 2 M aqueous potassium carbonate(3.08 mL, 6.16 mmol). The solution was degassed by applying vacuum andthen purging with nitrogen (3 times). To the reaction mixture was addedpalladium tetrakis (0.178 g, 0.154 mmol) and the flask was heated at100° C. under nitrogen for 36 hours. Water (5 mL) was added and themixture was extracted with ethyl acetate. The combined organics wereconcentrated and chromatographed (0-100% ethyl acetate/hexanes) to givetert-butyl(3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (705mg, 2.215 mmol, 71.9% yield) as a yellow solid and tert-butyl(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate (242 mg, 0.870 mmol,28.2% yield) as a yellow solid.

tert-Butyl(3-cyclopropyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp156.5-158.0; ¹H NMR (400 MHz, CDCl₃) δ 8.73 (s, 1H), 8.30 (d, J=2.5 Hz,1H), 8.27 (s, 1H), 7.76 (dt, J=9.8, 2.4 Hz, 1H), 6.43 (s, 1H), 1.55 (s,9H), 1.01-0.91 (m, 4H); ESIMS m/z 319 ([M+H]⁺).

(1-(5-Fluoropyridin-3-yl)-1H-pyrazol-4-yl)carbamate: mp 121.0-123.0° C.;¹H NMR (300 MHz, CDCl₃) δ 8.78 (s, 1H), 8.37 (s, 1H), 8.28 (s, 1H), 7.81(d, J=9.6 Hz, 1H), 7.59 (s, 1H), 6.44 (s, 1H), 1.53 (s, 9H). ESIMS m/z278 ([M]⁺).

Compounds 340 and 404 were prepared as described in Example 33.

Example 34 Preparation of tert-butyl(3-ethyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)(methyl)carbamate(Compound 408)

To a N₂-purged solution of tert-butyl(1-(5-fluoropyridin-3-yl)-3-vinyl-1H-pyrazol-4-yl)(methyl)carbamate(0.730 g, 2.293 mmol) in methanol (15.29 ml) was added 10% palladium oncarbon (0.036 g, 0.339 mmol). The reaction was purged with hydrogen andrun under 80 psi of hydrogen at room temperature for 60 hours. Thereaction gave less than 20% conversion. The reaction mixture wasfiltered through celite, concentrated, and redissolved in ethyl acetate(4 mL) and transferred to a bomb. The reaction was heated at 50° C. at600 psi of hydrogen for 20 hours. The reaction was only 50% complete.Methanol (1 mL) and 10% palladium on carbon (36 mg) were added, and thereaction was heated at 80° C. at 650 psi of hydrogen for 20 hours. Thereaction was filtered through celite and concentrated to give tert-butyl(3-ethyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)(methyl)carbamate (616mg, 1.923 mmol, 84% yield) as yellow oil: IR (thin film) 1692 cm⁻¹; ¹HNMR (300 MHz, CDCl₃) δ 8.71 (t, J=1.4 Hz, 1H), 8.35 (d, J=2.6 Hz, 1H),7.83 (dt, J=9.5, 2.3 Hz, 2H), 3.18 (s, 3H), 2.65 (q, J=7.5 Hz, 2H), 1.44(s, 9H), 1.25 (t, J=7.1 Hz, 3H); EIMS m/z 320.

Example 35 Preparation ofN-(1-(5-fluoropyridin-3-yl)-3-formyl-1H-pyrazol-4-yl)isobutyramide(Compound 560)

To a solution ofN-(1-(5-fluoropyridin-3-yl)-3-vinyl-1H-pyrazol-4-yl)isobutyramide (0.706g, 2.57 mmol) in tetrahydrofuran (12.87 ml) and water (12.87 ml) wasadded osmium tetroxide (0.164 ml, 0.026 mmol). After 10 minutes at roomtemperature, sodium periodate (1.101 g, 5.15 mmol) was added in portionsover 3 minutes and the resulting solution was stirred at roomtemperature. After 18 hours, the solution was poured into 10 mL waterand was extracted with 3×10 mL dichloromethane. The combined organiclayers were dried, concentrated and chromatographed (0-100% ethylacetate/hexanes) to giveN-(1-(5-fluoropyridin-3-yl)-3-formyl-1H-pyrazol-4-yl)isobutyramide (626mg, 2.266 mmol, 88% yield) as a yellow solid: mp 140.0-142.0° C.; ¹H NMR(300 MHz, CDCl₃) δ 10.12 (s, 1H), 9.14 (s, 1H), 8.90 (d, J=2.0 Hz, 1H),8.82 (s, 1H), 8.51 (d, J=2.5 Hz, 1H), 7.92 (dt, J=9.2, 2.4 Hz, 1H), 2.65(dt, J=13.8, 6.9 Hz, 1H), 1.31 (d, J=6.9 Hz, 6H); ESIMS m/z 277([M+H]⁺).

Compound 369 was prepared in accordance with the procedures disclosed inExample 35.

Example 36 Preparation ofN-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)isobutyramide(Compound 435) andN-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)isobutyramide (Compound 436)

To a solution ofN-(1-(5-fluoropyridin-3-yl)-3-formyl-1H-pyrazol-4-yl)isobutyramide(0.315 g, 1.140 mmol) in methanol (5.70 ml) at 0° C. was added sodiumborohydride (0.086 g, 2.280 mmol). The reaction was stirred at 0° C. for2 hours, and room temperature for 20 hours. 0.5 M HCl was added, thereaction was neutralized with saturated aqueous sodium bicarbonate, andthe mixture was extracted with dichloromethane. The organic phases wereconcentrated and chromatographed (0-100% ethyl acetate/hexanes) to giveN-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)isobutyramide(180 mg, 0.647 mmol, 56.7%) as a white solid andN-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)isobutyramide (9 mg, 0.036mmol, 3.18%) as a white solid.

N-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)isobutyramide:mp 144.0-146.0° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.74 (d, J=1.1 Hz, 1H),8.64 (s, 1H), 8.37-8.29 (m, 2H), 7.74 (dt, J=9.5, 2.3 Hz, 1H), 4.95 (d,J=3.0 Hz, 2H), 3.21-3.06 (m, 1H), 2.63-2.48 (m, 1H), 1.26 (d, J=6.9 Hz,6H); ESIMS m/z 279 ([M+H]⁺).

N-(1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)isobutyramide: IR (thinfilm) 1659 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.79 (d, J=1.2 Hz, 1H), 8.60(s, 1H), 8.38 (d, J=2.5 Hz, 1H), 7.81 (dt, J=9.5, 2.3 Hz, 1H), 7.68 (s,1H), 7.54 (s, 1H), 2.63-2.51 (m, 1H), 1.28 (d, J=6.9 Hz, 6H); ESIMS m/z249 ([M+H]⁺).

Example 37 Preparation ofN-(3-(chloromethyl)-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)isobutyramide(Compound 561)

To a solution ofN-(1-(5-fluoropyridin-3-yl)-3-(hydroxymethyl)-1H-pyrazol-4-yl)isobutyramide(0.100 g, 0.359 mmol) in dichloromethane (3.59 ml) was added thionylchloride (0.157 ml, 2.151 mmol). The reaction was stirred at roomtemperature for 2 hours. Saturated aqueous sodium bicarbonate was added,and the mixture was extracted with dichloromethane. The combined organicphases were washed with brine and concentrated to giveN-(3-(chloromethyl)-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)isobutyramide(100 mg, 0.337 mmol, 94% yield) as a white solid: mp 172.0-177.0° C.; ¹HNMR (400 MHz, CDCl₃) δ 8.79 (s, 1H), 8.67 (s, 1H), 8.40 (s, 1H), 7.80(dt, J=9.4, 2.3 Hz, 1H), 7.42 (s, 1H), 4.77 (s, 2H), 2.63 (hept, J=6.9Hz, 1H), 1.30 (d, J=6.9 Hz, 6H); ESIMS m/z 298 ([M+H]⁺).

Example 38 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methoxyacetamide(Compound 512) (see also Example 11)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine,2HCl (0.130 g, 0.502 mmol) and in DCM (2.508 ml) was addedN-ethyl-N-isopropylpropan-2-amine (0.257 ml, 1.505 mmol) followed by2-methoxyacetyl chloride (0.109 g, 1.003 mmol) and the reaction mixturewas stirred at ambient temperature for 16 hours. The reaction wasquenched by the addition of saturated sodium bicarbonate. The organiclayer was extracted with DCM. The organic layer was dried over sodiumsulfate, filtered, concentrated and purified using silica gelchromatography (0-100% ethyl acetate/hexanes) to yield the titlecompound as a pale yellow oil (0.12 g, 77%): IR (thin film) 3514, 3091,2978, 1676 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.96 (d, J=2.4 Hz, 1H), 8.63(d, J=3.8 Hz, 1H), 8.09-8.03 (m, 1H), 7.99 (s, 1H), 7.47 (dd, J=8.3, 4.8Hz, 1H), 3.88 (s, 2H), 3.77-3.65 (m, 2H), 3.40 (s, 3H), 1.18 (t, J=7.2Hz, 3H); ESIMS m/z 295 ([M+H]⁺).

Compounds 71, 478, 481, 483-484, and 543 were prepared in accordancewith the procedures disclosed in Example 38.

Example 39 Preparation ofN-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-(methylthio)butanamide(Compound 182) and(Z)-N-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methylbut-2-enamide(Compound 183)

To a solution 2-methyl-3-(methylthio)butanoic acid (0.154 g, 1.039 mmol)in dichloromethane (1 mL) at room temperature was added 1 drop ofdimethylformamide. Oxalyl dichloride (0.178 ml, 2.078 mmol) was addeddropwise and the reaction was stirred at room temperature overnight. Thesolvent was removed under reduced pressure. The residue was redissolvedin dichloromethane (1 mL) and the solvent was removed under reducedpressure. The residue was redissolved in dichloromethane (0.5 mL) andthe solution was added to a solution of3-chloro-N-ethyl-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-amine (0.100 g,0.416 mmol) and 4-dimethylaminopyridine (0.254 g, 2.078 mmol) indichloromethane (1.5 mL) and stirred at room temperature overnight. Thesolvent was removed under reduced pressure and the residue was purify bychromatography (0-100% ethyl acetate/hexanes) to giveN-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-(methylthio)butanamide(34 mg, 0.092 mmol, 22.06%) as a faint yellow oil and(Z)-N-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methylbut-2-enamide(38 mg, 0.118 mmol, 28.3% yield) as a yellow oil.

N-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-(methylthio)butanamide:IR (thin film) 1633 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.79 (d, J=2.0 Hz,0.66H), 8.77 (d, J=2.0 Hz, 0.33H), 8.50 (d, J=2.6 Hz, 0.33H), 8.49 (d,J=2.5 Hz, 0.66H), 8.08 (s, 0.66H), 7.95 (s, 0.33H), 7.92-7.81 (m, 1H),4.03-3.46 (m, 2H), 3.03-2.78 (m, 1H), 2.59-2.33 (m, 1H), 2.04 (s, 2H),2.02 (s, 1H), 1.32 (d, J=6.7 Hz, 1H), 1.27 (d, J=6.2 Hz, 1H), 1.23 (d,J=6.9 Hz, 2H), 1.18-1.12 (m, 5H); ESIMS m/z 371 ([M]⁺).

(Z)-N-(3-chloro-1-(5-fluoropyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methylbut-2-enamide:¹H NMR (400 MHz, CDCl₃) δ 8.73 (d, J=2.0 Hz, 1H), 8.46 (d, J=2.4 Hz,1H), 7.87 (d, J=4.9 Hz, 1H), 7.84 (dt, J=9.2, 2.4 Hz, 1H), 5.93-5.76 (m,1H), 3.73 (q, J=7.1 Hz, 2H), 1.72 (s, 3H), 1.58 (dd, J=6.9, 0.9 Hz, 3H),1.17 (t, J=7.1 Hz, 3H); ESIMS m/z 323 ([M]⁺).

Compounds 70, 180-181, 389-392, 397-398, 405-406, 427-429, 432, 456,482, 521-522, 532-534, 555, and 589 were prepared from the correspondingintermediates and starting materials in accordance with the proceduresdisclosed in Example 39.

Example 40 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-methyl-2-(methylthio)acetamide(Compound 337)

To an ice cold solution of 2-(methylthio)acetic acid (0.092 g, 0.863mmol) in DCM (2 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.111g, 0.863 mmol) followed by isobutyl chloroformate (0.099 ml, 0.767mmol). Stirring was continued for 10 minutes. Next, the mixed anhydridewas added to a solution of3-chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.08 g, 0.383mmol) in DCM (0.66 mL) and the reaction mixture was stirred at ambienttemperature for 2 hours. The reaction mixture was concentrated andpurified using reverse phase C-18 column chromatography (0-100%CH₃CN/H₂O) to yield the title compound as a pale yellow oil (0.075 g,66%): ¹H NMR (400 MHz, CDCl₃) δ 8.95 (d, J=2.5 Hz, 1H), 8.62 (dd, J=4.8,1.4 Hz, 1H), 8.13 (s, 1H), 8.04 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.50-7.43(m, 1H), 3.26 (s, 3H), 3.12 (s, 2H), 2.24 (s, 3H); ¹³C NMR (101 MHz,CDCl₃) δ 170.00, 148.61, 140.15, 140.03, 135.68, 126.56, 126.42, 125.33,124.15, 37.16, 34.94, 16.22; ESIMS m/z 297 ([M+H]⁺).

Compounds 335, 336, and 542 were prepared in accordance with theprocedures disclosed in Example 40.

Example 41 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-oxobutanamide(Compound 499)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine,HCl (259 mg, 1 mmol) and ethyl 2-methyl-3-oxobutanoate (144 mg, 1.000mmol) in dioxane (1 mL) was added2,3,4,6,7,8-hexahydro-1H-pyrimido[1,2-a]pyrimidine (181 mg, 1.30 mmol)and the mixture was heated in a microwave (CEM Discover) at 150° C. for1.5 h, with external IR-sensor temperature monitoring from the bottom ofthe vessel. LCMS (ELSD) indicated a 40% conversion to the desiredproduct. The mixture was diluted with ethyl acetate (50 mL) andsaturated aqueous NH₄Cl (15 mL), and the organic phase was separated.The aqueous phase was extracted with ethyl acetate (20 mL) and thecombined organic phase was washed with brine, dried over MgSO₄ andconcentrated in vacuo to give an oily residue. This residue was purifiedon silica gel eluting with mixtures of ethyl acetate and hexanes to giveN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-oxobutanamide(37 mg, 11% yield, 96% purity) as a colorless oil: ¹H NMR (400 MHz,CDCl₃) δ 9.02-8.92 (dd, J=2.6, 0.8 Hz, 1H), 8.68-8.60 (dd, J=4.8, 1.5Hz, 1H), 8.09-7.98 (m, 1H), 7.96-7.87 (s, 1H), 3.87-3.58 (d, J=3.0 Hz,2H), 3.49-3.38 (m, 1H), 2.16-2.08 (s, 3H), 1.39-1.32 (d, J=7.0 Hz, 3H),1.22-1.13 (m, 3H); EIMS (m/z) 321 ([M+1]⁺), 319 ([M−1]⁻).

Example 42 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylcyclopropanecarboxamide(Compound 538)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-aminemonohydrochloride (0.10 g, 0.0.38 mmol) in dichloroethane (0.75 ml) wasadded cyclopropanecarboxylic acid (0.03 g, 0.38 mmol) and4-N,N-dimethylaminopyridine (0.14 g, 1.15 mmol) followed by1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.14 g,0.77 mmol). The reaction was stirred at room temperature overnight. Thereaction mixture was concentrated to dryness and the crude product waspurified by reverse phase silica gel chromatography eluting with 0-50%acetonitrile/water to give a white solid (0.03 g, 25%); mp 111-119° C.;¹H NMR (400 MHz, CDCl₃) δ 8.96 (d, J=2.5 Hz, 1H), 8.63-8.59 (m, 1H),8.06 (ddd, J=8.3, 2.6, 1.4 Hz, 1H), 8.01 (s, 1H), 7.46 (dd, J=8.3, 4.7Hz, 1H), 3.73 (q, J=7.2 Hz, 2H), 1.46 (ddd, J=12.6, 8.1, 4.7 Hz, 1H),1.16 (t, J=7.2 Hz, 3H), 1.04 (t, J=3.7 Hz, 2H), 0.71 (dd, J=7.7, 3.0 Hz,2H); ESIMS m/z 291 ([M+H]).

Compounds 69, 516, 524, 546, 558-559, 582-588, 593, and 594 wereprepared from the appropriate acids in accordance with the proceduresdisclosed in Example 42.

Example 43 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)-N-(3-(methylthio)propanoyl)propanamide(Compound 407)

To a solution ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(methylthio)propanamide(0.216 g, 0.728 mmol) in DCE (2.91 ml) in a 10 mL vial was added2-methyl-3-(methylthio)propanoyl chloride (0.244 g, 1.601 mmol). Thevial was capped and placed in a Biotage Initiator microwave reactor for3 hours at 100° C., with external IR-sensor temperature monitoring fromthe side of the vessel. The crude mixture was concentrated and purifiedusing reverse phase C-18 column chromatography (0-100%acetonitrile/water) to yield the title compound as a pale yellow oil (67mg, 22%): IR (thin film) 2916 and 1714 cm⁻¹; ¹H NMR (300 MHz, CDCl₃) δ8.96-8.92 (d, J=2.7 Hz, 1H), 8.64-8.59 (dd, J=4.9, 1.4 Hz, 1H),8.07-7.99 (m, 2H), 7.50-7.40 (dd, J=8.4, 4.8 Hz, 1H), 3.39-3.28 (m, 1H),3.10-2.99 (td, J=7.2, 3.9 Hz, 2H), 2.96-2.86 (dd, J=13.2, 8.7 Hz, 1H),2.86-2.79 (t, J=7.3 Hz, 2H), 2.58-2.48 (dd, J=13.1, 5.8 Hz, 1H),2.14-2.12 (s, 3H), 2.09-2.06 (s, 3H), 1.30-1.26 (d, J=6.9 Hz, 3H); ESIMSm/z 413 ([M+H]⁺).

Compounds 383, 410, 433, 437, 451, 470, 530 and 531 were prepared inaccordance with the procedures disclosed in Example 43.

Example 44 Preparation ofN-[3-chloro-1-(3-pyridyl)pyrazol-4-yl]-2,2-dideuterio-N-ethyl-3-methylsulfanyl-propanamide(Compound 393)

To a 7 mL vial was added3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (111 mg, 0.5 mmol),2,2-dideuterio-3-methylsulfanyl-propanoic acid (58.0 mg, 0.475 mmol) andfollowed by DCM (Volume: 2 mL). The solution was stirred at 0° C. Thenthe solution of DCC (0.500 mL, 0.500 mmol, 1.0M in DCM) was added. Thesolution was allowed to warm up to 25° C. slowly and stirred at 25° C.overnight. White precipitate formed during the reaction. The crudereaction mixture was filtered through a cotton plug and purified bysilica gel chromatography (0-100% EtOAc/hexane) to giveN-[3-chloro-1-(3-pyridyl)pyrazol-4-yl]-2,2-dideuterio-N-ethyl-3-methylsulfanyl-propanamide(97 mg, 0.297 mmol, 59.4% yield) as a colorless oil: ¹H NMR (400 MHz,CDCl₃) δ 8.96 (d, J=2.4 Hz, 1H), 8.63 (dd, J=4.6, 0.9 Hz, 1H), 8.06(ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.52-7.40 (m, 1H), 3.72 (q,J=7.2 Hz, 2H), 2.78 (s, 2H), 2.06 (s, 3H), 1.17 (t, J=7.2 Hz, 3H); ESIMSm/z 327 ([M+H]⁺); IR (Thin film) 1652 cm⁻¹.

Compounds 394, 396, and 471-473 were prepared from the correspondingintermediates and starting materials in accordance with the proceduresdisclosed in Example 44.

Example 45 Preparation of1-ethyl-3-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)urea (Compound 145)

To a solution of 3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.1 g,0.574 mmol) in DCM (5.74 ml) was added ethyl isocyanate (0.041 g, 0.574mmol) and the reaction mixture was stirred at ambient temperature for 40minutes. The reaction mixture had turned from a clear solution to asuspension with white solid material. The reaction mixture wasconcentrated and purified using silica gel chromatography (0-20%MeOH/DCM) to yield the title compound as a white solid (0.135 g, 95%):mp 197-200° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.94 (d, J=2.3 Hz, 1H),8.48-8.37 (m, 1H), 8.32 (s, 1H), 7.94 (d, J=8.3 Hz, 1H), 7.52 (br s,1H), 7.41-7.25 (m, 1H), 5.79 (br s, 1H), 3.33-3.23 (m, 2H), 2.29 (d,J=2.9 Hz, 3H), 1.16 (dd, J=8.7, 5.7 Hz, 3H); ESIMS m/z 246 ([M+H]⁺), 244([M−H]⁻).

Compounds 169-171, 221-222, 255-257, 278-280, 297-302, 318-322, 334,345, 348, 375-377, 385-387, and 411-413 were prepared in accordance withthe procedures disclosed in Example 45.

Example 46 Preparation of3-butyl-1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-1-ethylurea(Compound 500)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine,2HCl (0.130 g, 0.502 mmol) in DCE (1.25 ml) was addedN-ethyl-N-isopropylpropane-2-amine (0.21 mL, 1.255 mmol) followed by1-isocyanatobutane (0.109 g, 1.104 mmol) and the reaction mixture wasstirred at ambient temperature for 16 hours. The reaction mixture wasconcentrated and purified using silica gel chromatography (0-20%MeOH/DCM) to yield the title compound as a beige solid (0.131 g, 77%):IR (thin film) 3326, 2959, 2931, 1648 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ8.95 (s, 1H), 8.62 (d, J=4.0 Hz, 1H), 8.08-8.01 (m, 1H), 7.97 (s, 1H),7.46 (dd, J=8.3, 4.7 Hz, 1H), 4.42-4.32 (m, 1H), 3.74-3.61 (m, 2H),3.27-3.15 (m, 2H), 1.49-1.37 (m, 2H), 1.37-1.22 (m, 2H), 1.19-1.12 (m,3H), 0.94-0.84 (m, 3H); ESIMS m/z 322 ([M+H]⁺).

Compounds 479-480, 501-504, 513, 518 and 519 were prepared according toExample 46.

Example 47 Preparation of1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)imidazolidin-2-one(Compound 374)

To a solution of1-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(2-chloroethyl)urea (0.1g, 0.333 mmol) in THF (6.66 ml) was added sodium hydride (8.00 mg, 0.333mmol) and the reaction mixture was stirred at ambient temperature for 30minutes. The reaction was quenched by the addition of a solution ofsaturated ammonium chloride and the product was extracted with ethylacetate (2×). The combined organic layers were dried over sodiumsulfate, filtered and concentrated. The product was a beige solid whichwas pure and did not need any further purification (63 mg, 72%): mp167-170° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.96 (d, J=2.2 Hz, 1H), 8.56 (dd,J=4.7, 1.4 Hz, 1H), 8.33 (s, 1H), 7.99 (ddd, J=8.3, 2.7, 1.4 Hz, 1H),7.40 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 5.00 (s, 1H), 4.14-4.07 (m, 2H),3.68-3.58 (m, 2H); ESIMS m/z 264 ([M+H]⁺).

Compound 349 was prepared in accordance with the procedures disclosed inExample 47.

Example 48 Preparation of S-tert-butyl(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)(ethyl)carbamothioate(Compound 514)

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine,2HCl (0.13 g, 0.502 mmol) in DCM (2.508 ml) was addedN-ethyl-N-isopropylpropan-2-amine (0.257 ml, 1.505 mmol) followed byS-tert-butyl carbonochloridothioate (0.153 g, 1.003 mmol). The reactionmixture was stirred at ambient temperature for 16 hours. The reactionwas quenched by the addition of saturated sodium bicarbonate. Theorganic layer was extracted with DCM. The organic layer was dried oversodium sulfate, filtered, concentrated and purified using silica gelcolumn chromatography (0-100% ethyl acetate/hexanes) to yield the titlecompound as a white solid (132 mg, 78%): mp 91-93° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.96 (d, J=2.5 Hz, 1H), 8.60 (dd, J=4.7, 1.4 Hz, 1H), 8.08-8.03(m, 1H), 7.97 (s, 1H), 7.47-7.41 (m, 1H), 3.69 (q, J=7.2 Hz, 2H), 1.47(s, 9H), 1.21-1.13 (m, 3H); ESIMS m/z 339 ([M+H]⁺).

Compounds 333, 338, 339, 346, 368 and 373 were prepared in accordancewith the procedures disclosed in Example 48.

Example 49 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-(methio)propanethioamide(Compound 364)

To a microwave reaction vessel was addedN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-2-methyl-3-(methio)propanamide(0.07 g, 0.22 mmol) in dichloroethane (1.87 mL) and Lawesson's reagent(0.05 g, 0.12 mmol). The vessel was capped and heated in a BiotageInitiator microwave reactor for 15 minutes at 130° C., with externalIR-sensor temperature monitoring from the side of the vessel. Thereaction was concentrated to dryness and the crude material was purifiedby silica gel chromatography (0-80% acetonitrile/water) to give thedesired product as a yellow oil (0.33 g, 44%): IR (thin film) 1436 cm⁻¹;¹H NMR (400 MHz, CDCl₃) δ 8.97 (d, J=2.5 Hz, 1H), 8.77-8.52 (m, 1H),8.11-7.89 (m, 2H), 7.60-7.38 (m, 1H), 4.62 (bs, 1H), 4.02 (bs, 1H),3.21-2.46 (m, 3H), 2.01 (s, 3H), 1.35-1.15 (m, 6H); ESIMS m/z 355([M+H]⁺).

Compounds 372, 438 and 548 were prepared in accordance with theprocedures disclosed in Example 49.

Example 50 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-4,4,4-trifluoro-3-(methylsulfinyl)butanamide(Compound 570)

To a 20 mL vial was addedN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-4,4,4-trifluoro-3-(methylthio)butanamide(82 mg, 0.209 mmol) and hexafluoroisopropanol (1.5 mL). Hydrogenperoxide (0.054 mL, 0.626 mmol, 35% solution in water) was added in oneportion and the solution was stirred at room temperature. After 3 hoursthe reaction was quenched with saturated sodium sulfite solution andextracted with EtOAc (3×20 mL). The combined organic layers were driedover sodium sulfate, concentrated and purified by chromatography (0-10%MeOH/DCM) to giveN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-4,4,4-trifluoro-3-(methylsulfinyl)butanamide (76 mg, 0.186 mmol, 89% yield) as white semi-solid: ¹H NMR(400 MHz, CDCl₃) δ 8.98 (d, J=2.3 Hz, 1H), 8.63 (td, J=4.8, 2.4 Hz, 1H),8.14-8.01 (m, 2H), 7.46 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 4.26 (dd, J=17.2,8.4 Hz, 1H), 3.89-3.61 (m, 2H), 3.01 (dd, J=17.6, 8.2 Hz, 1H), 2.77 (s,2H), 2.48 (dd, J=17.7, 3.3 Hz, 1H), 1.19 (t, J=7.2 Hz, 3H) (only oneisomer shown); ESIMS m/z 409 ([M+H]⁺); IR (Thin film) 1652 cm⁻¹.

Compound 571 was prepared from the corresponding intermediates andstarting materials in accordance with the procedures disclosed inExample 50.

Example 51 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(methylsulfinyl)propanamide(Compound 362)

ToN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(methylthio)propanamide(0.08 g, 0.24 mmol) in glacial acetic acid (0.82 mL) was added sodiumperborate tetrahydrate (0.05 g, 0.25 mmol), and the mixture was heatedat 60° C. for 1 hour. The reaction mixture was carefully poured into aseparatory funnel containing saturated aqueous NaHCO₃ resulting in gasevolution. When the gas evolution had ceased, ethyl acetate was addedand the layers were separated. The aqueous layer was extracted twicewith ethyl acetate, and all the organic layers were combined, dried overMgSO₄, filtered and concentrated under reduced pressure. The crudematerial was purified by silica gel chromatography (0-10%methanol/dichloromethane) to give the desired product as a clear oil(0.03 g, 40%): IR (thin film) 1655 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.95(t, J=9.2 Hz, 1H), 8.63 (dd, J=4.7, 1.4 Hz, 1H), 8.20-7.86 (m, 2H),7.59-7.33 (m, 1H), 3.73 (ddt, J=20.5, 13.4, 6.8 Hz, 2H), 3.23-3.06 (m,1H), 2.94-2.81 (m, 1H), 2.74-2.62 (m, 2H), 2.59 (s, 3H), 1.25-1.07 (m,3H); ESIMS m/z 341 ([M+H]⁺).

Compounds 101-102, 218, 328, 330, and 494 were prepared from theappropriate sulfides in accordance with the procedures disclosed inExample 51.

Example 52 Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(methylsulfonyl)propanamide(Compound 363)

ToN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethyl-3-(methylthio)propanamide(0.08 g, 0.25 mmol) in glacial acetic acid (0.85 mL) was added sodiumperborate tetrahydrate (0.11 g, 0.52 mmol), and the mixture was heatedat 60° C. for 1 hour. The reaction mixture was carefully poured into aseparatory funnel containing saturated aqueous NaHCO₃ resulting in gasevolution. When the gas evolution had ceased, ethyl acetate was addedand the layers were separated. The aqueous layer was extracted twicewith ethyl acetate, and all the organic layers were combined, dried overMgSO₄, filtered and concentrated under reduced pressure. The crudeproduct was purified by silica gel column chromatography (0 to 10%methanol/dichloromethane) to give the desired product as a clear oil(0.04, 47%): (thin film) 1661 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.95 (t,J=11.5 Hz, 1H), 8.64 (dd, J=4.8, 1.4 Hz, 1H), 8.17-7.96 (m, 2H),7.59-7.39 (m, 1H), 3.73 (d, J=7.0 Hz, 2H), 3.44 (dd, J=22.5, 15.7 Hz,2H), 2.96 (s, 3H), 2.71 (t, J=6.9 Hz, 2H), 1.18 (dd, J=8.8, 5.5 Hz, 3H);ESIMS m/z 357 ([M+H]⁺).

Compounds 103, 104, 219, 329, 331 and 495 were prepared from theappropriate sulfides in accordance with the procedures disclosed inExample 52.

Example 53 Preparation ofN-(3-methyl-1-(3-fluoropyridin-5-yl)-1H-pyrazol-4-yl)N-ethyl-2-methyl-(3-oxido-λ⁴-sulfanylidenecyanamide)(methyl)propanamide(Compound 250)

To a solution ofN-ethyl-N-(1-(5-fluoropyridin-3-yl)-3-methyl-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide(0.30 g, 0.89 mmol) in dichloromethane (3.57 mL) at 0° C. was addedcyanamide (0.07 g, 1.78 mmol) and iodobenzenediacetate (0.31 g, 0.98mmol) and subsequently stirred at room temperature for 1 hour. Thereaction was concentrated to dryness and the crude material was purifiedby silica gel column chromatography (10% methanol/ethyl acetate) to givethe desired sulfilamine as a light yellow solid (0.28 g, 85%). To asolution of 70% mCPBA (0.25 g, 1.13 mmol) in ethanol (4.19 mL) at 0° C.was added a solution of potassium carbonate (0.31 g, 2.26 mmol) in water(4.19 mL) and stirred for 20 minutes after which a solution ofsulfilamine (0.28 g, 0.75 mmol) in ethanol (4.19 mL) was added in oneportion. The reaction was stirred for 1 hour at 0° C. The excess mCPBAwas quenched with 10% sodium thiosulfite and the reaction wasconcentrated to dryness. The residue was purified by silica gelchromatography (0-10% methanol/dichloromethane) to give the desiredproduct as a clear oil (0.16 g, 56%): IR (thin film) 1649 cm⁻¹; ¹H NMR(400 MHz, CDCl₃) δ 8.80 (dd, J=43.8, 10.1 Hz, 1H), 8.51-8.36 (m, 1H),8.11 (d, J=38.7 Hz, 1H), 7.96-7.77 (m, 1H), 4.32-3.92 (m, 2H), 3.49-3.11(m, 6H), 2.32 (s, 3H), 1.27-1.05 (m, 6H); ESIMS m/z 393 ([M+H]⁺).

Example 54 Preparation ofN-ethyl-4,4,4-trifluoro-3-methoxy-N-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide(Compound 276)

To a solution ofN-ethyl-4,4,4-trifluoro-3-hydroxy-N-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide(184 mg, 0.448 mmol) in DMF (3 mL) stirring at 0° C. was added sodiumhydride (26.9 mg, 0.673 mmol). The solution was stirred at 0° C. for 0.5hour. Then iodomethane (0.034 mL, 0.538 mmol) was added and ice bath wasremoved and the mixture was stirred at 25° C. overnight. Reaction wasworked up by slow addition of water and further diluted with 20 mL ofwater, then extracted with 4×20 mL of EtOAc. The combined organic layerswere washed with water, dried over Na₂SO₄ and concentrated. Silica Gelchromatography (0-100% EtOAc/hexane) gaveN-ethyl-4,4,4-trifluoro-3-methoxy-N-(3-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-(trifluoromethyl)butanamide(52 mg, 0.123 mmol, 27.3% yield) as a white solid: mp=83-86° C.; ¹H NMR(400 MHz, CDCl₃) δ 8.94 (d, J=2.5 Hz, 1H), 8.59 (dd, J=4.7, 1.3 Hz, 1H),8.01 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.85 (s, 1H), 7.44 (ddd, J=8.3, 4.8,0.6 Hz, 1H), 4.00 (brs, 1H), 3.73 (s, 3H), 3.39 (brs, 1H), 2.86 (s, 2H),2.26 (s, 3H), 1.16 (t, J=7.1 Hz, 3H); ESIMS m/z 425 ([M+H]⁺); IR (Thinfilm) 1664 cm⁻¹.

Compound 327 was prepared from the corresponding intermediates andstarting materials in accordance with the procedures disclosed inExample 54.

Example 55 Step 1: Preparation ofN-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide

A solution ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide(0.150 g, 0.483 mmol) in N,N-dimethylformamide (2.413 ml) was cooled to0° C. Sodium hydride (0.039 g, 0.965 mmol, 60% dispersion) was added atand the reaction was stirred at 0° C. for 30 minutes.(2-Bromoethoxy)(tert-butyl)dimethylsilane (0.231 g, 0.965 mmol) wasadded, the ice bath was removed, and the reaction was stirred at roomtemperature for 2 hours. The reaction was heated at 65° C. for 1.5 hoursand then cooled to room temperature. Brine was added and the mixture wasextracted with dichloromethane. The combined organic phases wereconcentrated and chromatographed (0-100% ethyl acetate/hexanes) to giveN-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide(0.120 g, 0.243 mmol, 50.4%) as an orange oil: IR (thin film) 1669 cm⁻¹;¹H NMR (400 MHz, CDCl₃) δ 8.88 (d, J=2.5 Hz, 1H), 8.55 (dd, J=4.7, 1.4Hz, 1H), 8.05 (s, 1H), 7.98 (ddd, J=8.3, 2.6, 1.4 Hz, 1H), 7.41 (ddd,J=8.4, 4.8, 0.5 Hz, 1H), 4.35-3.06 (m, 4H), 2.86-2.73 (m, 1H), 2.73-2.59(m, 1H), 2.41 (dd, J=12.8, 5.7 Hz, 1H), 1.94 (s, 3H), 1.11 (d, J=6.7 Hz,3H), 0.80 (s, 9H), 0.00 (s, 3H), −0.01 (s, 3H); ESIMS m/z 470 ([M+H]⁺).

Example 55 Step 2: Preparation ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-2-methyl-3-(methylthio)propanamide(Compound 535)

To a solution ofN-(2-((tert-butyldimethylsilyl)oxy)ethyl)-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamide(0.180 g, 0.384 mmol) in tetrahydrofuran (1.54 ml) was addedtetrabutylammonium fluoride (0.201 g, 0.767 mmol) and the reaction wasstirred at room temperature for 2 hours. Brine was added and the mixturewas extracted with ethyl acetate. The combined organic phases wereconcentrated and chromatographed (0-100% water/acetonitrile) to giveN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-2-methyl-3-(methylthio)propanamideas a white oil (0.081 g, 0.217 mmol, 56.5%): IR (thin film) 3423, 1654cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.00 (d, J=2.5 Hz, 1H), 8.62 (dd, J=4.7,1.2 Hz, 1H), 8.25 (s, 1H), 8.07 (ddd, J=8.3, 2.4, 1.3 Hz, 1H), 7.47 (dd,J=8.3, 4.7 Hz, 1H), 4.47-3.70 (m, 3H), 3.65-3.09 (m, 2H), 2.91-2.68 (m,2H), 2.48 (dd, J=12.4, 5.0 Hz, 1H), 2.01 (s, 3H), 1.18 (d, J=6.5 Hz,3H); ESIMS m/z 356 ([M+H]⁺).

Example 56 Preparation of2-(N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamido)ethylacetate (Compound 547)

To a solution ofN-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-(2-hydroxyethyl)-2-methyl-3-(methylthio)propanamide(0.045 g, 0.127 mmol) in dichloromethane (1.27 ml) was addedN,N-dimethylpyridin-4-amine (0.023 g, 0.190 mmol) and triethylamine(0.019 g, 0.190 mmol) followed by acetyl chloride (0.015 g, 0.190 mmol).The reaction was stirred at room temperature overnight. Water was addedand the mixture was extracted with dichloromethane. The combined organicphases were concentrated and chromatographed (0-100% ethylacetate/hexanes) to give2-(N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-2-methyl-3-(methylthio)propanamido)ethylacetate as a yellow oil (0.015 g, 0.034 mmol, 26.8%): IR (thin film)1739, 1669 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.97 (d, J=2.3 Hz, 1H), 8.64(dd, J=4.7, 1.4 Hz, 1H), 8.15 (s, 1H), 8.04 (ddd, J=8.3, 2.7, 1.4 Hz,1H), 7.47 (ddd, J=8.3, 4.8, 0.7 Hz, 1H), 4.50-3.40 (m, 4H), 2.84 (dd,J=12.7, 8.9 Hz, 1H), 2.78-2.63 (m, 1H), 2.46 (dd, J=12.7, 5.4 Hz, 1H),2.03 (s, 3H), 2.01 (s, 3H), 1.16 (d, J=6.6 Hz, 3H); ESIMS m/z 398([M+H]⁺).

Example 57 Preparation of 2,2-dideuterio-3-methylsulfanyl-propanoic acid

To a 100 mL round bottom flask was added 3-(methylthio)propanoic acid (3g, 24.96 mmol), followed by D₂O (23 mL) and KOD (8.53 mL, 100 mmol) (40%wt solution in D₂O), the solution was heated to reflux overnight. NMRshowed ca. 95% D at alpha-position. The reaction was cooled down andquenched with concentrated HCl until pH<2. White precipitate appeared inaqueous layer upon acidifying. Reaction mixture was extracted with 3×50mL EtOAc, the combined organic layers were dried over Na₂SO₄,concentrated in vacuo to almost dryness. 100 mL hexane was added and thesolution was concentrated again to give2,2-dideuterio-3-methylsulfanyl-propanoic acid as a colorless oil (2.539g, 20.78 mmol, 83%): IR (Thin film) 3430, 1704 cm⁻¹; ¹H NMR (400 MHz,CDCl₃) δ 2.76 (s, 2H), 2.14 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 178.28,38.14-28.55 (m), 28.55, 15.51; EIMS m/z 122.

2-Deuterio-2-methyl-3-methylsulfanyl-propanoic acid was prepared asdescribed in Example 57 to afford a colorless oil (3.62 g, 26.8 mmol,60.9%): IR (Thin film) 2975, 1701 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ11.39-10.41 (brs, 1H), 2.88-2.79 (d, J=13.3 Hz, 1H), 2.61-2.53 (d,J=13.3 Hz, 1H), 2.16-2.09 (s, 3H), 1.32-1.25 (s, 3H); ¹³C NMR (101 MHz,CDCl₃) δ 181.74, 39.74-39.02 (m), 37.16, 16.50, 16.03; EIMS m/z 135.

Example 58 Preparation of2-methyl-3-(trideuteriomethylsulfanyl)propanoic acid

To a 50 mL round bottom flask was added 3-mercapto-2-methylpropanoicacid (5 g, 41.6 mmol), followed by MeOH (15 mL), the solution wasstirred at 25° C. Potassium hydroxide (5.14 g, 92 mmol) was added slowlyas the reaction is exothermic. Iodomethane-d₃ (6.63 g, 45.8 mmol) wasadded slowly and then the reaction mixture was heated at 65° C.overnight. The reaction was worked up by addition of 2 N HCl until themixture was acidic. It was then extracted with EtOAc (4×50 mL) and thecombined organic layers were dried over Na₂SO₄, concentrated andpurified with flash chromatography, eluted with 0-80% EtOAc/hexane togive 2-methyl-3-(trideuteriomethylsulfanyl)propanoic acid (4.534 g, 33.0mmol, 79%) as colorless oil: IR (Thin film) 3446, 1704 cm⁻¹; ¹H NMR (400MHz, CDCl₃) δ 2.84 (dd, J=13.0, 7.1 Hz, 1H), 2.80-2.66 (m, 1H), 2.57(dd, J=13.0, 6.6 Hz, 1H), 1.30 (d, J=7.0 Hz, 3H); EIMS m/z 137.

Example 59 Preparation of 2-hydroxy-3-(methylthio)propanoic acid

Sodium methanethiolate (4.50 g, 64.2 mmol) was added at 25° C. to asolution of 3-chloro-2-hydroxypropanoic acid (2 g, 16.06 mmol) in MeOH(120 mL). The reaction mixture was heated at reflux for 8 hours, thencooled to 25° C. The precipitate was removed by filtration and thefiltrate was evaporated. The residue was acidified to pH 2 with 2 N HCl,extracted with EtOAc (3×30 mL), combined organic layers were dried withNa₂SO₄, concentrated to give 2-hydroxy-3-(methylthio)propanoic acid as awhite solid, (1.898 g, 13.94 mmol, 87% yield): mp 55-59° C.; IR (Thinfilm) 2927, 1698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 6.33 (s, 3H), 4.48 (dd,J=6.3, 4.2 Hz, 1H), 3.02 (dd, J=14.2, 4.2 Hz, 1H), 2.90 (dd, J=14.2, 6.3Hz, 1H), 2.20 (s, 3H); EIMS m/z 136.

Example 60 Preparation of 2-methoxy-3-(methylthio)propanoic acid

To a stirred solution of sodium hydride (0.176 g, 4.41 mmol) in DMF (5mL) was added a solution of 2-hydroxy-3-(methylthio)propanoic acid (0.25g, 1.836 mmol) in 1 mL DMF at 25° C. and stirred for 10 min Vigorousbubbling was observed upon addition of NaH. Then iodomethane (0.126 mL,2.020 mmol) was added and the solution was stirred at 25° C. overnight.The reaction was quenched by addition of 2 N HCl, extracted with 3×10 mLof EtOAc, the combined organic layers were washed with water (2×20 mL),concentrated and purified by column chromatography, eluted with 0-100%EtOAc/hexane, gave 2-methoxy-3-(methylthio)propanoic acid (126 mg, 0.839mmol, 45.7% yield) as colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 9.10 (s,1H), 4.03 (dd, J=6.9, 4.4 Hz, 1H), 3.51 (s, 3H), 2.98-2.93 (m, 1H), 2.86(dd, J=14.1, 6.9 Hz, 1H), 2.21 (s, 3H); EIMS m/z 150.

Example 61 Preparation of 2-(acetylthiomethyl)-3,3,3-trifluoropropanoicacid

To a 50 mL round bottom flask was added 2-(trifluoromethyl)acrylic acid(6 g, 42.8 mmol), followed by thioacetic acid (4.59 ml, 64.3 mmol). Thereaction was slightly exothermic. The mixture was then stirred at 25° C.overnight. NMR showed some starting material (˜30%). One more equiv ofthioacetic acid was added and the mixture was heated at 95° C. for 1hour, then allowed to cool to room temperature. Mixture was purified byvacuum distillation at 2.1-mm Hg, fraction distilled at 80-85° C. wasmostly thioacetic acid, fraction distilled at 100-110° C. was almostpure product, contaminated by a nonpolar impurity (by TLC). It was againpurified by flash chromatography (0-20% MeOH/DCM), to give2-(acetylthiomethyl)-3,3,3-trifluoropropanoic acid (7.78 g, 36.0 mmol,84% yield) as colorless oil, which solidified under high vacuum to givea white solid: mp 28-30° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.52 (brs, 1H),3.44 (dt, J=7.5, 3.5 Hz, 2H), 3.20 (dd, J=14.9, 11.1 Hz, 1H), 2.38 (s,3H); ¹³C NMR (101 MHz, CDCl₃) δ 194.79, 171.14, 123.44 (q, J=281.6 Hz),50.47 (q, J=27.9 Hz), 30.44, 24.69 (q, J=2.6 Hz); ¹⁹F NMR (376 MHz,CDCl₃) δ −67.82.

Example 62 Preparation of 3,3,3-trifluoro-2-(methylthiomethyl)propanoicacid

To a solution of 2-(acetylthiomethyl)-3,3,3-trifluoropropanoic acid (649mg, 3 mmol) in MeOH (5 mL) stirring at 25° C. was added pellets ofpotassium hydroxide (421 mg, 7.50 mmol) in four portions over 5 minutes.Reaction was exothermic. Then MeI was added in once, the reactionmixture was then heated at 65° C. for 18 hours. The reaction was thencooled down and quenched with 2N HCl until acidic, and the aqueous layerextracted with chloroform (4×20 mL). Combined organic layer was dried,concentrated in vacuo, purified with flash chromatography (0-20%MeOH/DCM), to give 3,3,3-trifluoro-2-(methylthiomethyl)propanoic acid(410 mg, 2.179 mmol, 72.6% yield) as a light yellow oil: ¹H NMR (400MHz, CDCl₃) δ 10.95 (s, 1H), 3.49-3.37 (m, 1H), 3.02 (dd, J=13.8, 10.8Hz, 1H), 2.90 (dd, J=13.8, 4.0 Hz, 1H), 2.18 (s, 3H); ¹³C NMR (101 MHz,CDCl₃) δ 172.04 (q, J=2.8 Hz), 123.55 (q, J=281.2 Hz), 50.89 (q, J=27.5Hz), 29.62 (q, J=2.3 Hz), 15.85; ¹⁹F NMR (376 MHz, CDCl₃) δ −67.98.

Example 63 Preparation of 3-(methylthio)pentanoic acid

S,S-dimethyl carbonodithioate (1.467 g, 12.00 mmol) was added withvigorous stirring to a solution of (E)-pent-2-enoic acid (2.002 g, 20mmol) in 30% KOH solution (prepared from potassium hydroxide (3.87 g, 69mmol) and Water (10 mL)). The reaction mixture was slowly heated to 90°C. over a period of 20-30 min Heating was continued for 3 hours beforethe reaction was cooled down to 25° C. and quenched slowly with HCl. Themixture was then extracted with DCM (3×30 mL), combined organic layerdried and concentrated to give 3-(methylthio)pentanoic acid (2.7 g,18.22 mmol, 91% yield) as light orange oil: IR (Thin film) 2975, 1701cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 2.92 (qd, J=7.3, 5.6 Hz, 1H), 2.63 (d,J=7.2 Hz, 2H), 2.08 (s, 3H), 1.75-1.51 (m, 2H), 1.03 (t, J=7.4 Hz, 3H);¹³C NMR (101 MHz, CDCl₃) δ 178.14, 43.95, 39.78, 27.04, 12.95, 11.29;EIMS m/z 148.

4-methyl-3-(methylthio)pentanoic acid was prepared as described inExample 63 and isolated as a colorless oil: IR (Thin film) 2960, 1704cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 2.88 (ddd, J=9.1, 5.4, 4.7 Hz, 1H), 2.68(dd, J=16.0, 5.5 Hz, 1H), 2.55 (dd, J=16.0, 9.1 Hz, 1H), 2.13 (s, 3H),2.01-1.90 (m, 1H), 1.03 (d, J=6.8 Hz, 3H), 0.99 (d, J=6.8 Hz, 3H); EIMSm/z 162.

Example 64 Preparation of ethyl 1-(hydroxymethyl)cyclopropanecarboxylate

A 1M solution of lithium aluminum tri-tert-butoxyhydride intetrahydrofuran (70.90 mL, 70.90 mmol) was added to a stirred solutionof diethyl cyclopropane-1,1′-dicarboxylate (6 g, 32.20 mmol) intetrahydrofuran (129 mL) at 23° C. The resulting solution was heated to65° C. and stirred for 24 h. The cooled reaction mixture was dilutedwith a 10% solution of sodium bisulfate (275 mL) and extracted withethyl acetate. The combined organic layers were dried (MgSO₄), filtered,and concentrated to dryness to give the desired product as a pale yellowoil (4.60, 91%): ¹H NMR (300 MHz, CDCl₃) δ 4.16 (q, J=7 Hz, 2H), 3.62(s, 2H), 2.60 (br s, 1H), 1.22-1.30 (m, 5H), 0.87 (dd, J=7, 4 Hz, 2H).

Example 65 Preparation of ethyl1-((methylsulfonyloxy)methyl)cyclopropanecarboxylate

Triethylamine (5.57 mL, 40.00 mmol) and methanesulfonyl chloride (2.85mL, 36.60 mmol) were sequentially added to a stirred solution of ethyl1-(hydroxymethyl)cyclopropanecarboxylate (4.80 g, 33.30 mmol) indichloromethane (83 mL) at 23° C. The resulting bright yellow solutionwas stirred at 23° C. for 20 h. The reaction mixture was diluted withwater and extracted with dichloromethane. The combined organic layerswere dried (MgSO₄), filtered, and concentrated to dryness to give thedesired product as a brown oil (6.92 g, 94%): ¹H NMR (300 MHz, CDCl₃) δ4.33 (s, 2H), 4.16 (q, J=7 Hz, 2H), 3.08 (s, 3H), 1.43 (dd, J=7, 4 Hz,2H), 1.26 (t, J=7 Hz, 3H), 1.04 (dd, J=7, 4 Hz, 2H).

Example 66 Preparation of ethyl1-(methylthiomethyl)cyclopropanecarboxylate

Sodium methanethiolate (4.36 g, 62.30 mmol) was added to a stirredsolution of ethyl 1-((methylsulfonyloxy)methyl)cyclopropanecarboxylate(6.92 g, 31.10 mmol) in N,N-dimethylformamide (62.30 mL) at 23° C. Theresulting brown suspension was stirred at 23° C. for 18 h. The reactionmixture was diluted with water and extracted with diethyl ether. Thecombined organic layers were dried (MgSO₄), filtered, and concentratedby rotary evaporation to afford the title compound as a brown oil (5.43g, 100%): ¹H NMR (300 MHz, CDCl₃) δ 4.14 (q, J=7 Hz, 2H), 2.83 (s, 2H),2.16 (s, 3H), 1.31 (dd, J=7, 4 Hz, 2H), 1.25 (t, J=7 Hz, 3H), 0.89 (dd,J=7, 4 Hz, 2H).

Example 67 Preparation of 1-(methylthiomethyl)cyclopropanecarboxylicacid

A 50% solution of sodium hydroxide (12.63 mL, 243 mmol) was added to astirred solution of ethyl 1-(methylthiomethyl)cyclopropanecarboxylate(5.43 g, 31.20 mmol) in absolute ethanol (62.30 mL) at 23° C. Theresulting solution was stirred at 23° C. for 20 h. The reaction mixturewas diluted with a 0.5 M solution of sodium hydroxide and washed withdichloromethane. The aqueous layer was acidified to pH≈1 withconcentrated hydrochloric acid and extracted with dichloromethane. Thecombined organic layers were dried (Na₂SO₄), filtered, and concentratedand concentrated to dryness to give the desired product as a light brownoil (2.10 g, 46%): ¹H NMR (300 MHz, CDCl₃) δ 2.82 (s, 2H), 2.17 (s, 3H),1.41 (dd, J=7, 4 Hz, 2H), 0.99 (dd, J=7, 4 Hz, 2H).

Example 68 Preparation of 2,2-dimethyl-3-(methylthio)propanoic acid

2,2-Dimethyl-3-(methylthio)propanoic acid can be prepared asdemonstrated in the literature (reference Musker, W. K.; et al. J. Org.Chem. 1996, 51, 1026-1029). Sodium methanethiolate (1.0 g, 14 mmol, 2.0equiv) was added to a stirred solution of 3-chloro-2,2-dimethylpropanoicacid (1.0 g, 7.2 mmol, 1.0 equiv) in N,N-dimethylformamide (3.7 mL) at0° C. The resulting brown suspension was allowed to warm to 23° C. andstirred for 24 h. The reaction mixture was diluted with a saturatedsolution of sodium bicarbonate (300 mL) and washed with diethyl ether(3×75 mL). The aqueous layer was acidified to pH≈1 with concentratedhydrochloric acid and extracted with diethyl ether (3×75 mL). Thecombined organic layers were dried (sodium sulfate), gravity filtered,and concentrated to afford a colorless oil (1.2 g, 99% crude yield). ¹HNMR (300 MHz, CDCl₃) δ 2.76 (s, 2H), 2.16 (s, 3H), 1.30 (s, 6H).

Example 69 Preparation of 4,4,4-trifluoro-3-(methylthio)butanoic acid

To a 100 mL round bottom flask was added (E)-4,4,4-trifluorobut-2-enoicacid (8 g, 57.1 mmol) and Methanol (24 mL), the solution was stirred ina water bath, then sodium methanethiolate (10.01 g, 143 mmol) was addedin three portions. Vigorous bubbling was observed, the mixture wasstirred at 25° C. overnight, NMR showed no more starting material. Tothe reaction mixture was added 2 N HCl until acidic. The mixture wasextracted with chloroform (5×50 mL), combined organic layer was driedover Na₂SO₄, concentrated in vacuo and further dried under high vacuumuntil there was no weight loss to give4,4,4-trifluoro-3-(methylthio)butanoic acid (10.68 g, 56.8 mmol, 99%yield) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 10.88 (s, 1H), 3.53(dqd, J=10.5, 8.3, 4.0 Hz, 1H), 2.96 (dd, J=16.9, 4.0 Hz, 1H), 2.65 (dd,J=16.9, 10.4 Hz, 1H), 2.29 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 175.78(s), 126.61 (q, J_(C-F)=278.8 Hz), 44.99 (q, J_(C-F)=30.3 Hz), 34.12 (d,J_(C-F)=1.7 Hz), 15.95 (s); EIMS m/z 162.

Example 70 Preparation of 3-methyl-3-methylsulfanyl-butyric acid

3-methyl-3-methylsulfanyl-butyric acid was made using the proceduresdisclosed in J. Chem Soc Perkin 1, 1992, 10, 1215-21).

Example 71 Preparation of 3-methylsulfanyl-butyric acid

3-Methylsulfanyl-butyric acid was made using the procedures disclosed inSynthetic Comm., 1985, 15 (7), 623-32.

Example 72 Preparation of tetrahydro-thiophene-3-carboxylic acid

Tetrahydro-thiophene-3-carboxylic acid was made using the proceduresdisclosed in Heterocycles, 2007, 74, 397-409.

Example 73 Preparation of 2-methyl-3-methylsulfanyl-butyric acid

2-Methyl-3-methylsulfanyl-butyric acid was made as described in J. ChemSoc Perkin 1, 1992, 10, 1215-21.

Example 74 Preparation of (1S,2S)-2-(methylthio)cyclopropanecarboxylicacid

(1S,2S)-2-(Methylthio)cyclopropanecarboxylic acid was made using theprocedures disclosed in Synthetic Comm., 2003, 33 (5); 801-807.

Example 75 Preparation of 2-(2-(methylthio)ethoxy)propanoic acid

2-(2-(Methylthio)ethoxy)propanoic acid was made as described in WO2007/064316 A1.

Example 76 Preparation of 2-((tetrahydrofuran-3-yl)oxy)propanoic acid

2-((Tetrahydrofuran-3-yl)oxy)propanoic acid was made as described in WO2007/064316 A1.

Example 77 Bioassays on Green Peach Aphid (“GPA”) (Myzus persicae)(MYZUPE)

GPA is the most significant aphid pest of peach trees, causing decreasedgrowth, shriveling of the leaves, and the death of various tissues. Itis also hazardous because it acts as a vector for the transport of plantviruses, such as potato virus Y and potato leafroll virus to members ofthe nightshade/potato family Solanaceae, and various mosaic viruses tomany other food crops. GPA attacks such plants as broccoli, burdock,cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce,macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, andzucchini, among other plants. GPA also attacks many ornamental cropssuch as carnation, chrysanthemum, flowering white cabbage, poinsettia,and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPAusing procedures described in the following example. In the reporting ofthe results, “Table 3: GPA (MYZUPE) and sweetpotato whitefly-crawler(BEMITA) Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 GPA (wingless adult and nymph stages) one day prior to chemicalapplication. Four pots with individual seedlings were used for eachtreatment. Test compounds (2 mg) were dissolved in 2 mL ofacetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm testcompound. The stock solutions were diluted 5× with 0.025% Tween 20 inH₂O to obtain the solution at 200 ppm test compound. A hand-heldaspirator-type sprayer was used for spraying a solution to both sides ofcabbage leaves until runoff. Reference plants (solvent check) weresprayed with the diluent only containing 20% by volume ofacetone/methanol (1:1) solvent. Treated plants were held in a holdingroom for three days at approximately 25° C. and ambient relativehumidity (RH) prior to grading. Evaluation was conducted by counting thenumber of live aphids per plant under a microscope. Percent Control wasmeasured by using Abbott's correction formula (W. S. Abbott, “A Methodof Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18(1925), pp. 265-267) as follows.Corrected % Control=100*(X−Y)/X

-   -   where    -   X=No. of live aphids on solvent check plants and    -   Y=No. of live aphids on treated plants

The results are indicated in the table entitled “Table 4. BiologicalData for GPA (MYZUPE) and sweetpotato whitefly-crawler (BEMITA)” (SeeTable Section).

Example 78 Insecticidal Test for Sweetpotato Whitefly-Crawler (Bemisiatabaci) (BEMITA) in Foliar Spray Assay

Cotton plants grown in 3-inch pots, with 1 small (3-5 cm) true leaf,were used as test substrate. The plants were placed in a room withwhitefly adults. Adults were allowed to deposit eggs for 2-3 days. Aftera 2-3 day egg-laying period, plants were taken from the adult whiteflyroom. Adults were blown off leaves using a hand-held Devilbiss sprayer(23 psi). Plants with egg infestation (100-300 eggs per plant) wereplaced in a holding room for 5-6 days at 82° F. and 50% RH for egg hatchand crawler stage to develop. Four cotton plants were used for eachtreatment. Compounds (2 mg) were dissolved in 1 mL of acetone solvent,forming stock solutions of 2000 ppm. The stock solutions were diluted10× with 0.025% Tween 20 in H₂O to obtain a test solution at 200 ppm. Ahand-held Devilbiss sprayer was used for spraying a solution to bothsides of cotton leaf until runoff. Reference plants (solvent check) weresprayed with the diluent only. Treated plants were held in a holdingroom for 8-9 days at approximately 82° F. and 50% RH prior to grading.Evaluation was conducted by counting the number of live nymphs per plantunder a microscope. Insecticidal activity was measured by using Abbott'scorrection formula and presented in “Table 4. Biological Data for GPA(MYZUPE) and sweetpotato whitefly-crawler (BEMITA)” (see column“BEMITA”):Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live nymphs on solvent check plants        -   Y=No. of live nymphs on treated plants            Pesticidally Acceptable Acid Addition Salts, Salt            Derivatives, Solvates, Ester Derivatives, Polymorphs,            Isotopes and Radionuclides

Molecules of Formula One may be formulated into pesticidally acceptableacid addition salts. By way of a non-limiting example, an amine functioncan form salts with hydrochloric, hydrobromic, sulfuric, phosphoric,acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic,succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic,benzenesulfonic, methanesulfonic, ethanesulfonic,hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally,by way of a non-limiting example, an acid function can form saltsincluding those derived from alkali or alkaline earth metals and thosederived from ammonia and amines. Examples of preferred cations includesodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By wayof a non-limiting example, a salt derivative can be prepared bycontacting a free base with a sufficient amount of the desired acid toproduce a salt. A free base may be regenerated by treating the salt witha suitable dilute aqueous base solution such as dilute aqueous sodiumhydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate.As an example, in many cases, a pesticide, such as 2,4-D, is made morewater-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with asolvent, such that the complex remains intact after the non-complexedsolvent is removed. These complexes are often referred to as “solvates.”However, it is particularly desirable to form stable hydrates with wateras the solvent.

Molecules of Formula One may be made into ester derivatives. These esterderivatives can then be applied in the same manner as the inventiondisclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs.Polymorphism is important in the development of agrochemicals sincedifferent crystal polymorphs or structures of the same molecule can havevastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Ofparticular importance are molecules having ²H (also known as deuterium)in place of ¹H.

Molecules of Formula One may be made with different radionuclides. Ofparticular importance are molecules having ¹⁴C.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus,certain molecules can be produced as racemic mixtures. It will beappreciated by those skilled in the art that one stereoisomer may bemore active than the other stereoisomers. Individual stereoisomers maybe obtained by known selective synthetic procedures, by conventionalsynthetic procedures using resolved starting materials, or byconventional resolution procedures. Certain molecules disclosed in thisdocument can exist as two or more isomers. The various isomers includegeometric isomers, diastereomers, and enantiomers. Thus, the moleculesdisclosed in this document include geometric isomers, racemic mixtures,individual stereoisomers, and optically active mixtures. It will beappreciated by those skilled in the art that one isomer may be moreactive than the others. The structures disclosed in the presentdisclosure are drawn in only one geometric form for clarity, but areintended to represent all geometric forms of the molecule.

Combinations

Molecules of Formula One may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withone or more compounds having acaricidal, algicidal, avicidal,bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal,nematicidal, rodenticidal, or virucidal properties. Additionally, themolecules of Formula One may also be used in combination (such as, in acompositional mixture, or a simultaneous or sequential application) withcompounds that are antifeedants, bird repellents, chemosterilants,herbicide safeners, insect attractants, insect repellents, mammalrepellents, mating disrupters, plant activators, plant growthregulators, or synergists. Examples of such compounds in the abovegroups that may be used with the Molecules of Formula Oneare—(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane,1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol,2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA,2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium,2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl,2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl,2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl,2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl,2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl,2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl,2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium,2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 21P,2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP,4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP,4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate,acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole,acibenzolar, acibenzolar-5-methyl, acifluorfen, acifluorfen-methyl,acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein,acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor,alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin,allethrin, allicin, allidochlor, allosamidin, alloxydim,alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin,alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin,amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron,aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl,amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole,ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos,anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone,antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam,asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl,azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin,azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate,barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl,benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl,benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin,benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos,benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap,bentaluron, bentazone, bentazone-sodium, benthiavalicarb,benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,benzadox-ammonium, benzalkonium chloride, benzamacril,benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzylbenzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin,beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl,bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin,bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac,bispyribac-sodium, bistrifluoron, bitertanol, bithionol, bixafen,blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid,brassinolide, brassinolide-ethyl, brevicomin, brodifacoum,brofenvalerate, brofluthrinate, bromacil, bromacil-lithium,bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos,bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT,bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxyniloctanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol,bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundymixture, busulfan, butacarb, butachlor, butafenacil, butamifos,butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron,butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos,cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide,calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor,captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam,carbendazim, carbendazim benzenesulfonate, carbendazim sulfite,carbetamide, carbofuran, carbon disulfide, carbon tetrachloride,carbophenothion, carbosulfan, carboxazole, carboxide, carboxin,carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartaphydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure,Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone,chlomethoxyfen, chloralose, chloramben, chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium,chloramben-sodium, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside,chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride,chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac,chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole,chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren,chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon,chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequatchloride, chlornidine, chlornitrofen, chlorobenzilate,chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron,chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin,chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron,chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos,chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II,cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide,cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop,clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,codlelure, colophonate, copper acetate, copper acetoarsenite, copperarsenate, copper carbonate, basic, copper hydroxide, copper naphthenate,copper oleate, copper oxychloride, copper silicate, copper sulfate,copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl,coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure,cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide,cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin,cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid,cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin,cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil,cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin,cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid,cyprosulfamide, cyromazine, cythioate, daimuron, dalapon,dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide,dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT,debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn,d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate,dicamba, dicamba-diglycolamine, dicamba-dimethylammonium,dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl,dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine,dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone,dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl,dichlormate, dichlormid, dichlorophen, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline,diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine,diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl,dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb,dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron,difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin,dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin,dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate,dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon,dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole,diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinosebacetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate,dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion,diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone,diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquatdibromide, disparlure, disul, disulfuram, disulfoton, disul-sodium,ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron,d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium,dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicinhydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure,doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone,edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothal, endothal-diammonium,endothal-dipotassium, endothal-disodium, endothion, endrin,enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron,ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol,ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethylformate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylenedibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos,fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan,fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl,fenoprop-butomethyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl,fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim,fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil,fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop,flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl,flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid,florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl,fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron,flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate,fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin,flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl,fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole,fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate,flupropanate-sodium, flupyradifurone, flupyrsulfuron,flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole,flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone,fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl,fluoroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole,flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil,flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen,fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde,formetanate, formetanate hydrochloride, formothion, formparanate,formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl,fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins,gliftor, glufosinate, glufosinate-ammonium, glufosinate-P,glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime,glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium, glyphosate-monoammonium,glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatineacetates, halacrinate, halfenprox, halofenozide, halosafen,halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD,heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexaflurate, hexylure, hexamide, hexazinone, hexylthiofos,hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo,hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide,hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil,imazalil nitrate, imazalil sulfate, imazamethabenz,imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr,imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate,iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan,indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane,iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium,iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate,ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos,isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin,isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl,isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos,japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid,jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenilehormone III, kadethrin, karbutilate, karetazan, karetazan-potassium,kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox,ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi,lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil,lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure,looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA,malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper,mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA,MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium,MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl,MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil,mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform,medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr,mefenpyr-diethyl, mefluidide, mefluidide-diolamine,mefluidide-potassium, megatomoic acid, menazon, mepanipyrim,meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride,mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron,mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone,metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron,metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron,methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole,methfuroxam, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,methometon, methomyl, methoprene, methoprotryne, methoquin-butyl,methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methylapholate, methyl bromide, methyl eugenol, methyl iodide, methylisothiocyanate, methylacetophos, methylchloroform, methyldymron,methylene chloride, methylmercury benzoate, methylmercury dicyandiamide,methylmercury pentachlorophenoxide, methylneodecanamide, metiram,metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos,mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox,mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron,monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquatdichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid,moxidectin, MSMA, muscalure, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyaceticacids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin,neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine,nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl,norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron,nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace,omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil,oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate,oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,oxymatrine, oxytetracycline, oxytetracycline hydrochloride,paclobutrazol, paichongding, para-dichlorobenzene, parafluoron,paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,penconazole, pencycuron, pendimethalin, penflufen, penfluoron,penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin,pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazineoxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl,phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea,phenylmercury acetate, phenylmercury chloride, phenylmercury derivativeof pyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb,phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram,picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,picloram-olamine, picloram-potassium, picloram-triethylammonium,picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl,pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim,polyoxorim-zinc, polythialan, potassium arsenite, potassium azide,potassium cyanate, potassium gibberellate, potassium naphthenate,potassium polysulfide, potassium thiocyanate, potassiumα-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, pretilachlor, primidophos, primisulfuron,primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl,prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb,prometon, prometryn, promurit, propachlor, propamidine, propamidinedihydrochloride, propamocarb, propamocarb hydrochloride, propanil,propaphos, propaquizafop, propargite, proparthrin, propazine,propetamphos, propham, propiconazole, propineb, propisochlor, propoxur,propoxycarbazone, propoxycarbazone-sodium, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarbhydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute,proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl,pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole,pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon,pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl,pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole,pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan,pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop,quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide,rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong,salicylanilide, sanguinarine, santonin, schradan, scilliroside,sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz,semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin,siduron, siglure, silafluofen, silatrane, silica gel, silthiofam,simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor,sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumorthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide,sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram,spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine,streptomycin, streptomycin sesquisulfate, strychnine, sulcatol,sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone,sulfuram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron,sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid,sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep,tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium,TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane,tetrachlorvinphos, tetraconazole, tetradifon, tetrafluoron,tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul,thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole,thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluoron,thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron,thiencarbazone, thiencarbazone-methyl, thifensulfuron,thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime,thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclamoxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate,thiohempa, thiomersal, thiometon, thionazin, thiophanate,thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap,thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium,thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil,tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad,tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadimefon, triadimenol, triafamone,tri-allate, triamiphos, triapenthenol, triarathene, triarimol,triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide,tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat,triclopyr, triclopyr-butotyl, triclopyr-ethyl,triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane,trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron,trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin,triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan,triptolide, tritac, triticonazole, tritosulfuron, trunc-call,uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin,valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate,vinclozolin, warfarin, warfarin-potassium, warfarin-sodium,xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols,xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin,zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram,zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone,α-multistriatin, and α-naphthaleneacetic acid. For more informationconsult the “COMPENDIUM OF PESTICIDE COMMON NAMES” located athttp://www.alanwood.net/pesticides/index.html. Also consult “THEPESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright 2006by British Crop Production Council, or its prior or more recenteditions.

Biopesticides

Molecules of Formula One may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more biopesticides. The term “biopesticide” is used for microbialbiological pest control agents that are applied in a similar manner tochemical pesticides. Commonly these are bacterial, but there are alsoexamples of fungal control agents, including Trichoderma spp. andAmpelomyces quisqualis (a control agent for grape powdery mildew).Bacillus subtilis are used to control plant pathogens. Weeds and rodentshave also been controlled with microbial agents. One well-knowninsecticide example is Bacillus thuringiensis, a bacterial disease ofLepidoptera, Coleoptera, and Diptera. Because it has little effect onother organisms, it is considered more environmentally friendly thansynthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinernema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are notlimited to, baculoviruses, bacteria and other prokaryotic organisms,fungi, protozoa and Microsproridia. Biologically derived insecticidesinclude, but not limited to, rotenone, veratridine, as well as microbialtoxins; insect tolerant or resistant plant varieties; and organismsmodified by recombinant DNA technology to either produce insecticides orto convey an insect resistant property to the genetically modifiedorganism. In one embodiment, the molecules of Formula One may be usedwith one or more biopesticides in the area of seed treatments and soilamendments. The Manual of Biocontrol Agents gives a review of theavailable biological insecticide (and other biology-based control)products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents(formerly the Biopesticide Manual) 3rd Edition. British Crop ProductionCouncil (BCPC), Farnham, Surrey UK.

Other Active Compounds

Molecules of Formula One may also be used in combination (such as in acompositional mixture, or a simultaneous or sequential application) withone or more of the following:

-   1.    3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   2.    3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;-   3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;-   4.    4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;-   5.    3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide;-   6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;-   7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;-   8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;-   9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;-   10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;-   11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;-   12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;-   13.    3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide;-   14.    N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone;-   15.    N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)    hydrazone nicotine;-   16.    O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methyl    thiocarbonate;-   17.    (E)-N-1-[2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;-   18.    1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol;-   19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl    mesylate; and-   20.    N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.    Synergistic Mixtures

Molecules of Formula One may be used with certain active compounds toform synergistic mixtures where the mode of action of such compoundscompared to the mode of action of the molecules of Formula One are thesame, similar, or different. Examples of modes of action include, butare not limited to: acetylcholinesterase inhibitor; sodium channelmodulator; chitin biosynthesis inhibitor; GABA and glutamate-gatedchloride channel antagonist; GABA and glutamate-gated chloride channelagonist; acetylcholine receptor agonist; acetylcholine receptorantagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinicacetylcholine receptor; Midgut membrane disrupter; oxidativephosphorylation disrupter, and ryanodine receptor (RyRs). Generally,weight ratios of the molecules of Formula One in a synergistic mixturewith another compound are from about 10:1 to about 1:10, in anotherembodiment from about 5:1 to about 1:5, and in another embodiment fromabout 3:1, and in another embodiment about 1:1.

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide can beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra low volume solutions. For further information onformulation types see “Catalogue of Pesticide Formulation Types andInternational Coding System” Technical Monograph n° 2, 5th Edition byCropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually selected from among the attapulgite clays, themontmorillonite clays, the diatomaceous earths, or the purifiedsilicates. Effective surfactants, comprising from about 0.5% to about10% of the wettable powder, are found among sulfonated lignins,condensed naphthalenesulfonates, naphthalenesulfonates,alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants suchas ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are selected from conventionalanionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums may also be added, to increase the density andviscosity of the aqueous carrier. It is often most effective to grindand mix the pesticide at the same time by preparing the aqueous mixtureand homogenizing it in an implement such as a sand mill, ball mill, orpiston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and compound and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. They canbe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules can be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one compound which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one non-ionic lipophilic surface-active agent,(2) at least one non-ionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers. Further information onthe embodiment is disclosed in U.S. patent publication 20070027034published Feb. 1, 2007, having patent application Ser. No. 11/495,228.For ease of use, this embodiment will be referred to as “OIWE”.

For further information consult “Insect Pest Management” 2nd Edition byD. Dent, copyright CAB International (2000). Additionally, for moredetailed information consult “Handbook of Pest Control—The Behavior,Life History, and Control of Household Pests” by Arnold Mallis, 9thEdition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface ofparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, non-ionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates. Tristyrylphenol ethoxylate phosphate esters are also used.Non-ionics such as alkylarylethylene oxide condensates and EO-PO blockcopolymers are sometimes combined with anionics as dispersing agents forsuspension concentrates. In recent years, new types of very highmolecular weight polymeric surfactants have been developed as dispersingagents. These have very long hydrophobic ‘backbones’ and a large numberof ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant.These high molecular weight polymers can give very good long-termstability to suspension concentrates because the hydrophobic backboneshave many anchoring points onto the particle surfaces. Examples ofdispersing agents used in agrochemical formulations are: sodiumlignosulfonates; sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol ethoxylate phosphate esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO-PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The types of surfactants usuallyused for solubilization are non-ionics, sorbitan monooleates, sorbitanmonooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennon-ionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersare usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, oil-in-water emulsions, suspoemulsions, and ultra lowvolume formulations, and to a lesser extent, granular formulations.Sometimes mixtures of solvents are used. The first main groups ofsolvents are aliphatic paraffinic oils such as kerosene or refinedparaffins. The second main group (and the most common) comprises thearomatic solvents such as xylene and higher molecular weight fractionsof C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful ascosolvents to prevent crystallization of pesticides when the formulationis emulsified into water. Alcohols are sometimes used as cosolvents toincrease solvent power. Other solvents may include vegetable oils, seedoils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are not limited to,montmorillonite, bentonite, magnesium aluminum silicate, andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations tofoam during mixing operations in production and in application through aspray tank. In order to reduce the tendency to foam, anti-foam agentsare often added either during the production stage or before fillinginto bottles. Generally, there are two types of anti-foam agents, namelysilicones and non-silicones. Silicones are usually aqueous emulsions ofdimethyl polysiloxane, while the non-silicone anti-foam agents arewater-insoluble oils, such as octanol and nonanol, or silica. In bothcases, the function of the anti-foam agent is to displace the surfactantfrom the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce theoverall environmental footprint of crop protection formulations. Greenagents are biodegradable and generally derived from natural and/orsustainable sources, e.g. plant and animal sources. Specific examplesare: vegetable oils, seed oils, and esters thereof, also alkoxylatedalkyl polyglucosides.

For further information, see “Chemistry and Technology of AgrochemicalFormulations” edited by D. A. Knowles, copyright 1998 by Kluwer AcademicPublishers. Also see “Insecticides in Agriculture andEnvironment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I.Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

Pests

In general, the molecules of Formula One may be used to control pestse.g. beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies,leafhoppers, ants, wasps, termites, moths, butterflies, lice,grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites,ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Anoplura. A non-exhaustive list of particulargenera includes, but is not limited to, Haematopinus spp., Hoplopleuraspp., Linognathus spp., Pediculus spp., and Polyplax spp. Anon-exhaustive list of particular species includes, but is not limitedto, Haematopinus asini, Haematopinus suis, Linognathus setosus,Linognathus ovillus, Pediculus humanus capitis, Pediculus humanushumanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used tocontrol pests in the Order Coleoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Acanthoscelides spp.,Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophoraspp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp.,Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp.,Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp.,Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp.,Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp.,Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp.,and Tribolium spp. A non-exhaustive list of particular species includes,but is not limited to, Acanthoscelides obtectus, Agrilus planipennis,Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus,Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum,Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata,Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi,Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinisnitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestespusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporausmarginatus, Dermestes lardarius, Dermestes maculatus, Epilachnavarivestis, Faustinus cubae, Hylobius pales, Hypera postica,Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata,Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus,Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolonthamelolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros,Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus,Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanustruncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius,Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Triboliumcastaneum, Tribolium confusum, Trogoderma variabile, and Zabrustenebrioides.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Dermaptera.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Blattaria. A non-exhaustive list ofparticular species includes, but is not limited to, Blattella germanica,Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana,Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa,Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Diptera. A non-exhaustive list of particulargenera includes, but is not limited to, Aedes spp., Agromyza spp.,Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp.,Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineuraspp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyzaspp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. Anon-exhaustive list of particular species includes, but is not limitedto, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens,Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis,Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineurabrassicae, Delia platura, Fannia canicularis, Fannia scalaris,Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans,Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Muscaautumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomyabetae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletismendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Hemiptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Adelges spp.,Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastesspp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp.,Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp.,Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp.,Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphumspp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp.,Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive listof particular species includes, but is not limited to, Acrosternumhilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicusdispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula,Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi,Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissusleucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicorynebrassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus,Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphisnoxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus,Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistusheros, Euschistus servus, Helopeltis antonii, Helopeltis theivora,Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus,Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus,Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium,Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata,Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettixcinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvatalugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis,Phylloxera vitifoliae, Physokermes piceae, Phytocoris californicus,Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus,Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes,Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi,Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobionavenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodesabutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Hymenoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Acromyrmex spp., Attaspp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp.,Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp.,Vespula spp., and Xylocopa spp. A non-exhaustive list of particularspecies includes, but is not limited to, Athalia rosae, Atta texana,Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis,Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsisrichtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Isoptera. A non-exhaustive list of particulargenera includes, but is not limited to, Coptotermes spp., Cornitermesspp., Cryptotermes spp., Heterotermes spp., Kalotermes spp.,Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermesspp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp.,and Zootermopsis spp. A non-exhaustive list of particular speciesincludes, but is not limited to, Coptotermes curvignathus, Coptotermesfrenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi,Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermessantonensis, Reticulitermes speratus, Reticulitermes tibialis, andReticulitermes virginicus.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Lepidoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Adoxophyes spp.,Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilospp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp.,Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp.,Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp.,Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp.,Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp.,Synanthedon spp., and Yponomeuta spp. A non-exhaustive list ofparticular species includes, but is not limited to, Achaea janata,Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana,Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella,Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archipsrosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes,Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposinaniponensis, Chlumetia transversa, Choristoneura rosaceana,Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydiacaryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydiapomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella,Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpuslignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella,Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoeciliaambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata,Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellulaundalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucopteracoffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotisalbicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti,Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta,Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata,Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemisheparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia,Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistiscitrella, Pieris rapae, Plathypena scabra, Plodia interpunctella,Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae,Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu,Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setoranitens, Sitotroga cerealella, Sparganothis pilleriana, Spodopteraexigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides,Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae,and Zeuzera pyrina.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Mallophaga. A non-exhaustive list ofparticular genera includes, but is not limited to, Anaticola spp.,Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., andTrichodectes spp. A non-exhaustive list of particular species includes,but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis,Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas,Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Orthoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Melanoplus spp., andPterophylla spp. A non-exhaustive list of particular species includes,but is not limited to, Anabrus simplex, Gryllotalpa africana,Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla,Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, andScudderia furcata.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Siphonaptera. A non-exhaustive list ofparticular species includes, but is not limited to, Ceratophyllusgallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalidesfelis, and Pulex irritans.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Thysanoptera. A non-exhaustive list ofparticular genera includes, but is not limited to, Caliothrips spp.,Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustivelist of particular sp. includes, but is not limited to, Frankliniellafusca, Frankliniella occidentalis, Frankliniella schultzei,Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothripscruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothripsrhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thripsorientalis, Thrips tabaci.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Thysanura. A non-exhaustive list ofparticular genera includes, but is not limited to, Lepisma spp. andThermobia spp.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Order Acarina. A non-exhaustive list of particulargenera includes, but is not limited to, Acarus spp., Aculops spp.,Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp.,Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp.,Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list ofparticular species includes, but is not limited to, Acarapis woodi,Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi,Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus,Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoidespteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychuscoffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi,Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalussanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychusurticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used tocontrol pest of the Order Symphyla. A non-exhaustive list of particularsp. includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula One may be used tocontrol pests of the Phylum Nematoda. A non-exhaustive list ofparticular genera includes, but is not limited to, Aphelenchoides spp.,Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp.,Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchusspp., and Radopholus spp. A non-exhaustive list of particular sp.includes, but is not limited to, Dirofilaria immitis, Heterodera zeae,Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus,Radopholus similis, and Rotylenchulus reniformis.

For additional information consult “HANDBOOK OF PEST CONTROL—THEBEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by ArnoldMallis, 9th Edition, copyright 2004 by GIE Media Inc.

Applications

Molecules of Formula One are generally used in amounts from about 0.01grams per hectare to about 5000 grams per hectare to provide control.Amounts from about 0.1 grams per hectare to about 500 grams per hectareare generally preferred, and amounts from about 1 gram per hectare toabout 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula One is applied can be any areainhabited (or maybe inhabited, or traversed by) a pest, for example:where crops, trees, fruits, cereals, fodder species, vines, turf andornamental plants, are growing; where domesticated animals are residing;the interior or exterior surfaces of buildings (such as places wheregrains are stored), the materials of construction used in building (suchas impregnated wood), and the soil around buildings. Particular cropareas to use a molecule of Formula One include areas where apples, corn,sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley,oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes,peppers, crucifers, pears, tobacco, almonds, sugar beets, beans andother valuable crops are growing or the seeds thereof are going to beplanted. It is also advantageous to use ammonium sulfate with a moleculeof Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity,or both, are reduced in an area. This can come about when: pestpopulations are repulsed from an area; when pests are incapacitated inor around an area; or pests are exterminated, in whole, or in part, inor around an area. Of course, a combination of these results can occur.Generally, pest populations, activity, or both are desirably reducedmore than fifty percent, preferably more than 90 percent. Generally, thearea is not in or on a human; consequently, the locus is generally anon-human area.

The molecules of Formula One may be used in mixtures, appliedsimultaneously or sequentially, alone or with other compounds to enhanceplant vigor (e.g. to grow a better root system, to better withstandstressful growing conditions). Such other compounds are, for example,compounds that modulate plant ethylene receptors, most notably1-methylcyclopropene (also known as 1-MCP). Furthermore, such moleculesmay be used during times when pest activity is low, such as before theplants that are growing begin to produce valuable agriculturalcommodities. Such times include the early planting season when pestpressure is usually low.

The molecules of Formula One can be applied to the foliar and fruitingportions of plants to control pests. The molecules will either come indirect contact with the pest, or the pest will consume the pesticidewhen eating leaf, fruit mass, or extracting sap, that contains thepesticide. The molecules of Formula One can also be applied to the soil,and when applied in this manner, root and stem feeding pests can becontrolled. The roots can absorb a molecule taking it up into the foliarportions of the plant to control above ground chewing and sap feedingpests.

Generally, with baits, the baits are placed in the ground where, forexample, termites can come into contact with, and/or be attracted to,the bait. Baits can also be applied to a surface of a building,(horizontal, vertical, or slant surface) where, for example, ants,termites, cockroaches, and flies, can come into contact with, and/or beattracted to, the bait. Baits can comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed onthe surface of a capsule. The size of the capsules can range fromnanometer size (about 100-900 nanometers in diameter) to micrometer size(about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resistcertain pesticides, repeated applications of the molecules of FormulaOne may be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying (for example by sprayingan area) the molecules of Formula One to a different portion of theplant. For example, control of foliar-feeding insects can be achieved bydrip irrigation or furrow application, by treating the soil with forexample pre- or post-planting soil drench, or by treating the seeds of aplant before planting.

Seed treatment can be applied to all types of seeds, including thosefrom which plants genetically modified to express specialized traitswill germinate. Representative examples include those expressingproteins toxic to invertebrate pests, such as Bacillus thuringiensis orother insecticidal toxins, those expressing herbicide resistance, suchas “Roundup Ready” seed, or those with “stacked” foreign genesexpressing insecticidal toxins, herbicide resistance,nutrition-enhancement, drought resistance, or any other beneficialtraits. Furthermore, such seed treatments with the molecules of FormulaOne may further enhance the ability of a plant to better withstandstressful growing conditions. This results in a healthier, more vigorousplant, which can lead to higher yields at harvest time. Generally, about1 gram of the molecules of Formula One to about 500 grams per 100,000seeds is expected to provide good benefits, amounts from about 10 gramsto about 100 grams per 100,000 seeds is expected to provide betterbenefits, and amounts from about 25 grams to about 75 grams per 100,000seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula One may beused on, in, or around plants genetically modified to expressspecialized traits, such as Bacillus thuringiensis or other insecticidaltoxins, or those expressing herbicide resistance, or those with“stacked” foreign genes expressing insecticidal toxins, herbicideresistance, nutrition-enhancement, or any other beneficial traits.

The molecules of Formula One may be used for controlling endoparasitesand ectoparasites in the veterinary medicine sector or in the field ofnon-human animal keeping. The molecules of Formula One are applied, suchas by oral administration in the form of, for example, tablets,capsules, drinks, granules, by dermal application in the form of, forexample, dipping, spraying, pouring on, spotting on, and dusting, and byparenteral administration in the form of, for example, an injection.

The molecules of Formula One may also be employed advantageously inlivestock keeping, for example, cattle, sheep, pigs, chickens, andgeese. They may also be employed advantageously in pets such as, horses,dogs, and cats. Particular pests to control would be fleas and ticksthat are bothersome to such animals. Suitable formulations areadministered orally to the animals with the drinking water or feed. Thedosages and formulations that are suitable depend on the species.

The molecules of Formula One may also be used for controlling parasiticworms, especially of the intestine, in the animals listed above.

The molecules of Formula One may also be employed in therapeutic methodsfor human health care. Such methods include, but are limited to, oraladministration in the form of, for example, tablets, capsules, drinks,granules, and by dermal application.

Pests around the world have been migrating to new environments (for suchpest) and thereafter becoming a new invasive species in such newenvironment. The molecules of Formula One may also be used on such newinvasive species to control them in such new environment.

The molecules of Formula One may also be used in an area where plants,such as crops, are growing (e.g. pre-planting, planting, pre-harvesting)and where there are low levels (even no actual presence) of pests thatcan commercially damage such plants. The use of such molecules in sucharea is to benefit the plants being grown in the area. Such benefits,may include, but are not limited to, improving the health of a plant,improving the yield of a plant (e.g. increased biomass and/or increasedcontent of valuable ingredients), improving the vigor of a plant (e.g.improved plant growth and/or greener leaves), improving the quality of aplant (e.g. improved content or composition of certain ingredients), andimproving the tolerance to abiotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticideundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, and international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by a third party on the product registrant's behalf, oftenusing a computer with a connection to the World Wide Web. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user or seller with productregistration approval. Thereafter, in that locality where the productregistration is granted and supported, such user or seller may use orsell such pesticide.

A molecule according to Formula One can be tested to determine itsefficacy against pests. Furthermore, mode of action studies can beconducted to determine if said molecule has a different mode of actionthan other pesticides. Thereafter, such acquired data can bedisseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not beused to interpret any portion hereof.

Table Section

TABLE 1 Compound number, appearance, and structure Compound No.Appearance Structure 1 yellow gum

2 yellow solid

3 yellow gum

4 yellow oil

5 yellow oil

6 yellow gum

7 yellow gum

8 yellow gum

9 beige gum

10 colorless gum

12 colorless glass

18 Brown oil

19 Yellow oil

20 Yellow oil

21 Yellow oil

22 clear oil

23 clear oil

24

25

26

27

28

29

30

31

32 Gold syrup

33 Brown solid

34 Off white solid

35 Off white solid

36 Off white solid

37 White solid

38 Off white solid

39 White solid

40 Pale yellow solid

41 Brown thick mass

42 Pale yellow semi solid

43 Pale yellow solid

44 White solid

45 Brown thick mass

46 Pale yellow thick mass

47 Pale yellow thick mass

48 Pale green thick mass

49 Pale yellow solid

50 Brown thick mass

51 Pale yellow thick mass

52 tan solid

53 White Solid

54 Clear Oil

55 White Semi Solid

56 Brown Solid

57 White Solid

58 Clear Oil

59 White Solid

60 White Solid

61 Light Yellow Solid

62 Clear Oil

63 Light Yellow Solid

64 White Solid

65 White Solid

66 White Semi Solid

67 Yellow Semi Solid

68 Clear Oil

69 Dark Brown Oil

70 Viscous Pale Yellow Oil

71 White Solid

72 White Semi Solid

73 White Semi Solid

74 Clear Oil

75 White Semi Solid

76 Clear Oil

77 White Solid

78 White Solid

79 White Solid

80 White Solid

81 White Solid

82 White Solid

83 White Solid

84 White Solid

85 Off-White Solid

86 Yellow Solid

87 Yellow Solid

88 White Solid

89 White Solid

90 Clear Oil

91 Faint Yellow Oil

92 Faint Yellow Oil

93 White Solid

94 Clear Oil

95 Clear Oil

96 Yellow Solid

97 Yellow Oil

98 Yellow Oil

99 Yellow Solid

100 Clear Oil

101 Clear Oil

102 Clear Oil

103 Clear Oil

104 Faint Yellow Oil

105 Off-White Solid

106 Faint Yellow Oil

107 White Solid

108 Clear Oil

109 Yellow Solid

110 Brown Oil

111 Yellow Solid

112 Brown Oil

113 Yellow Oil

114 Brown Oil

115 Light Brown Solid

116 Yellow Solid

117 Yellow Oil

118 Brown Oil

119 Brown Oil

120 Brown Oil

121 Off-White Solid

122 Faint Yellow Solid

123 Clear Oil

124 Yellow Solid

125 White Solid

126 Yellow Oil

127 Yellow Oil

128 Neon Yellow Oil

129 Neon Yellow Oil

130 Pink Solid

131 Red Oil

132 Yellow Oil

133 Yellow Oil

134 Clear Oil

135 Off-While Solid

136 Yellow Oil

137 Yellow Oil

138 Yellow Oil

139 Faint Yellow Oil

140 Faint Yellow

141 Light Yellow Solid

142 Clear Oil

143 Colorless Oil

144 Colorless Oil

145 White Solid

146 Gray Oil

147 Colorless Oil

148 White Solid

149 Yellow Solid

150 White Solid

151 Clear Oil

152 Clear Oil

153 White Solid

154 Faint Orange Oil

155 Clear Oil

156 Clear Oil

157 Clear Oil

158 Clear Oil

159 Clear Oil

160 White Solid

161 Brown Oil

162 Light Brown Solid

163 White Solid

164 White Solid

165 White Solid

166 Yellow Oil

167 Grey Oil

168 Faint Purple Oil

169 White Solid

170 While Solid

171 White Solid

172 White Solid

173 White Solid

174 Clear Oil

175 White Solid

176 Yellow Oil

177 White Solid

178 Yellow Oil

179 White Solid

180 Yellow Solid

181 Faint Yellow Oil

182 Faint Yellow Oil

183 Yellow Oil

184 Colorless Oil

185 White Solid

186 White Solid

187 Yellow Solid

188 Yellow Oil

189 Yellow Oil

190 Yellow Oil

191 Yellow Oil

192 Yellow Oil

193 Yellow Solid

194 White Solid

195 White Solid

196 Tan Solid

197 White Solid

198 Tan Solid

199 Gold Solid

200 Yellow Oil

201 Gold Oil

202 White Semi Solid

203 Yellow Oil

204 Yellow Oil

205 Yellow Oil

206 Yellow Oil

207 White Solid

208 White Solid

209 Yellow Oil

210 Yellow Oil

211 Yellow Oil

212 Yellow Oil

213 Yellow Oil

214 Yellow Oil

215 Clear Oil

216 Cream Colored Solid

217 Clear Oil

218 Clear Oil

219 Clear Oil

220 Yellow Oil

221 White Solid

222 White Solid

223 White Solid

224 Colorless Oil

225 Yellow Oil

226 White Solid

227 White Solid

228 Colorless Oil

229 Colorless Oil

230 Colorless Oil

231 Colorless Oil

232 White Solid

233 White Solid

234 White Solid

235 Colorless Oil

236 Colorless Oil

237 White Solid

238 Colorless Oil

239 Colorless Oil

240 White Solid

241 Colorless Oil

242 Colorless Oil

243 Colorless Oil

244 White Solid

245 White Solid

246 Colorless Oil

247 White Solid

248 Colorless Oil

249 White Solid

250 Clear Oil

251 Brown Oil

252 Off White Solid

253 Off White Solid

254 Brown Oil

255 White Solid

256 White Solid

257 White Solid

258 Brown Oil

259 White Solid

260 Colorless Oil

261 White Solid

262 White Solid

263 Colorless Oil

264 Colorless Oil

265 White Solid

266 Colorless Semi-Solid

267 Colorless Oil

268 White Solid

269 White Solid

270 White Solid

271 Colorless Oil

272 White Solid

273 Colorless Oil

274 Colorless Oil

275 White Solid

276 White Solid

277 Brown Amorphous Solid

278 White Solid

279 White Solid

280 White Solid

281 Orange Foam

282 Colorless Oil

283 Colorless Oil

284 Colorless Oil

285 Clear Oil

286 Yellow Oil

287 Yellow Oil

288 Yellow Oil

289 Dark Yellow Oil

290 Yellow Oil

291 Clear Oil

292 Tan Oil

293 Clear Oil

294 Yellow Oil

295 White Semi-Solid

296 Colorless Oil

297 White Solid

298 White Solid

299 White Solid

300 White Solid

301 White Solid

302 White Solid

303 Colorless Oil

304 Light Yellow Oil

305 White Solid

306 Grey Solid

307 Colorless Oil

308 Colorless Oil

309 Colorless Oil

310 Light Yellow Semi-Solid

311 Colorless Oil

312 White Solid

313 Light Yellow Solid

314 Faint Yellow Oil

315 Faint Yellow Oil

316 Faint Yellow Oil

317 White Solid

318 Brown Solid

319 Brown Solid

320 Yellow Solid

321 Yellow Solid

322 Yellow Solid

323 Colorless Oil

324 White Solid

325 White Solid

326 Colorless Oil

327 White Solid

328 White Foam

329 White Foam

330 White Foam

331 White Foam

332 Clear Yellow Oil

333 Clear Oil

334 Light Brown Solid

335 White Solid

336 White Solid

337 Pale Yellow Oil

338 Clear Oil

339 Clear Oil

340 White Solid

341 Yellow Oil

342 Yellow Oil

343 Yellow Oil

344 Yellow Oil

345 Yellow Solid

346 White Solid

347 Pale Yellow Oil

348 Brown Solid

349 Beige Solid

350 Colorless Oil

351 White Solid

352 Yellow Solid

353 Yellow Oil

354 Yellow Oil

355 Yellow Solid

356 Yellow Oil

357 Yellow Oil

358 Off-White Solid

359 Off White Solid

360 White Solid

361 Tan Solid

362 Clear Oil

363 Clear Oil

364 Yellow Oil

365 Yellow Oil

366 Yellow Oil

367 Clear Oil

368 White Solid

369 Light Brown Oil

370 Colorless Gum

371 Colorless Gum

372 Yellow Oil

373 White Solid

374 Beige Solid

375 White Solid

376 White Solid

377 White Solid

378 White Solid

379 White Solid

380 White Solid

381 White Solid

382 Clear Oil

383 Pale Yellow Oil

384 Colorless Oil

385 White Solid

386 White Solid

387 White Solid

388 White Solid

389 Colorless Oil

390 Off-White Solid

391 Colorless Oil

392 Colorless Oil

393 Colorless Oil

394 Colorless Oil

395 Pink Solid

396 Colorless Oil

397 Colorless Oil

398 White Solid

399 White Solid

400 Yellow Oil

401 Yellow Oil

402 Yellow Oil

403 Yellow Oil

404 Yellow Solid

405 Colorless Oil

406 Colorless Oil

407 Pale Yellow Oil

408 Yellow Oil

409 White Solid

410 Orange Oil

411 Beige Solid

412 White Solid

413 White Solid

414 Yellow Oil

415 Off-White Solid

416 Yellow Oil

417 Yellow Oil

418 Yellow Solid

419 Yellow Oil

420 Yellow Oil

421 Light Yellow Oil

422 Light Yellow Oil

423 Light Yellow Oil

424 Tan Solid

425 Colorless Oil

426 Colorless Oil

427 Yellow Oil

428 Yellow Oil

429 Yellow Oil

430 Light Yellow Oil

431 White Solid

432 Yellow Oil

433 Yellow Oil

434 White Solid

435 White Solid

436 White Solid

437 Yellow Oil

438 Yellow Oil

439 White Solid

440 White Solid

441 Yellow Solid

442 White Solid

443 White Solid

444 Brown Solid

445 Brown Solid

446 Yellow Solid

447 Dark Oil

448 Brown Solid

449 Tan Solid

450 White Oil

451 Colorless Gum

452 Yellow Oil

453 Colorless Oil

454 White Solid

455 Colorless Gum

456 Yellow Oil

457 White Oil

458 White Solid

459 Colorless Oil

460 White Solid

461 Colorless Gum

462 White Solid

463 White Solid

464 Colorless Gum

465 White Solid

466 White Solid

467 Colorless Gum

468 Light Yellow Solid

469 White Solid

470 Light Yellow Oil

471 Light Yellow Oil

472 Light Yellow Oil

473 Light Purple Solid

474 Yellow Oil

475 Light Yellow Oil

476 White Solid

477 Off-white Solid

478 Clear Oil

479 Beige Solid

480 White Solid

481 Light Yellow Oil

482 Beige Solid

483 Clear Viscous Oil

484 Clear Viscous Oil

485 White Oil

486 Off White Solid

487 Off-white Gum

488 Light Yellow Solid

489 Yellow Solid

490 Light Yellow Oil

491 Light Yellow Oil

492 White Solid

493 Light Orange Oil

494 Yellow Oil

495 Clear Oil

496 Light Yellow Oil

497 Light Yellow Oil

498 Light Yellow Oil

499 Colorless Oil

500 Beige Solid

501 White Solid

502 Thick Yellow Oil

503 Beige Solid

504 Beige Solid

505 Colorless Gum

506 Clear Colorless Oil

507 Clear Colorless Oil

508 Clear Colorless Oil

509 Pale Yellow Gum

510 Yellow Oil

511 White Oil

512 Pale Yellow Oil

513 Thick Clear Oil

514 White Solid

515 White Oil

516 Dark Brown Oil

517 White Solid

518 White Solid

519 White Solid

520 Brown Gum

521 Beige Solid

522 White Solid

523 Yellow Solid

524 Light Brown Solid

525 Faint Yellow Solid

526 Faint Yellow Solid

527 Yellow Oil

528 Light Brown Oil

529 Faint Yellow Solid

530 Clear Oil

531 Yellow Oil

532 White Solid

533 Orange Oil

534 Red Oil

535 White Oil

536 White Solid

537 Clear Oil

538 White Solid

539 Clear Oil

540 Clear Oil

541 Light Yellow Oil

542 Colorless Oil

543 White Solid

544 White Solid

545 White Fluffy Solid

546 Brown Solid

547 Yellow Oil

548 White-Yellow Oil

549 Colorless Oil

550 Colorless Oil

551 Colorless Oil

552 Colorless Oil

553 Colorless Oil

554 Colorless Oil

555 Yellow Oil

556 Pale Yellow Oil

557 Faint Yellow Oil

558 Faint Yellow Oil

559 Faint Yellow Oil

560 Yellow Solid

561 White Solid

562 Brown Gum

563 Pale Yellow Gum

564 Pale Yellow Gum

565 Pale Yellow Gum

566 Pale Yellow Gum

567 Off-white Solid

568 Pale Yellow Gum

569 Colorless Oil

570 White Semi-Solid

571 White Semi-Solid

572 Colorless Oil

573 Colorless Oil

574 Colorless Oil

575 Colorless Oil

576 Colorless Oil

577 Colorless Oil

578 Colorless Oil

579 Colorless Oil

580 Colorless Oil

581 Colorless Solid

582 Clear Oil

583 Brown Oil

584 Dark Yellow Oil

585 White Solid

586 Yellow Solid

587 Purple Solid

588 Dark Yellow Oil

589 Colorless Solid

590 Brown Solid

591 Light Yellow Solid

592 Brown Oil

593 Brown Oil

594 Faint Yellow Solid

595 White Solid

Lengthy table referenced here US08815271-20140826-T00001 Please refer tothe end of the specification for access instructions.

Lengthy table referenced here US08815271-20140826-T00002 Please refer tothe end of the specification for access instructions.

Lengthy table referenced here US08815271-20140826-T00003 Please refer tothe end of the specification for access instructions.

LENGTHY TABLES The patent contains a lengthy table section. A copy ofthe table is available in electronic form from the USPTO web site(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US08815271B2). Anelectronic copy of the table will also be available from the USPTO uponrequest and payment of the fee set forth in 37 CFR 1.19(b)(3).

We claim:
 1. A composition comprising a molecule according to

wherein (a) A is

(b) R1 is H; (c) R2 is H; (d) R3 is H; (e) R4 is Cl; (f) R5 is H; (g) R6is methyl or ethyl; (h) R7 is O; (i) R8 is (substituted or unsubstitutedC₁-C₆ alkyl)-S(O)_(n)-(substituted or unsubstituted C₁-C₆ alkyl) whereinsaid substituents on said substituted alkyls are selected from F, Cl,Br, I; (k) n is 0, 1, or 2; and (l) X is CR_(n1) where R_(n1) is H or F.2. A composition according to claim 1 wherein said molecule has one ofthe following structures


3. A composition according to claim 1 further comprising: (a) one ormore compounds having acaricidal, algicidal, avicidal, bactericidal,fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal,rodenticidal, or virucidal properties; or (b) one or more compounds thatare antifeedants, bird repellents, chemosterilants, herbicide safeners,insect attractants, insect repellents, mammal repellents, matingdisrupters, plant activators, plant growth regulators, or synergists; or(c) both (a) and (b).
 4. A composition according to claim 1 whereinfurther comprising one or more compounds selected from:(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane,1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol,2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA,2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium,2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl,2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butomethyl, 2,4,5-T-butotyl,2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl,2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium,2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D,2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl,2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium,2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl,2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium,2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl,2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl,2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl,2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium,2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium,2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP,2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP,4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP,4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate,8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate,acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole,acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl,acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein,acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor,alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin,allethrin, allicin, allidochlor, allosamidin, alloxydim,alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin,alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin,amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron,aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl,aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium,aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl,amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole,ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos,anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone,antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam,asulam-potassium, asulam-sodium, athidathion, atraton, atrazine,aureofungin, aviglycine, aviglycine hydrochloride, azaconazole,azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl,azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin,azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate,barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl,benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl,benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin,benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos,benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap,bentaluron, bentazone, bentazone-sodium, benthiavalicarb,benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox,benzadox-ammonium, benzalkonium chloride, benzamacril,benzamacril-isobutyl, benzamorf, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid,benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzylbenzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin,beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox,bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl,bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin,bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac,bispyribac-sodium, bistrifluoron, bitertanol, bithionol, bixafen,blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid,brassinolide, brassinolide-ethyl, brevicomin, brodifacoum,brofenvalerate, brofluthrinate, bromacil, bromacil-lithium,bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos,bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT,bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil,bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxyniloctanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol,bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundymixture, busulfan, butacarb, butachlor, butafenacil, butamifos,butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron,butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin,butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos,cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide,calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor,captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam,carbendazim, carbendazim benzenesulfonate, carbendazim sulfite,carbetamide, carbofuran, carbon disulfide, carbon tetrachloride,carbophenothion, carbosulfan, carboxazole, carboxide, carboxin,carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartaphydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure,Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone,chlomethoxyfen, chloralose, chloramben, chloramben-ammonium,chloramben-diolamine, chloramben-methyl, chloramben-methylammonium,chloramben-sodium, chloramine phosphorus, chloramphenicol,chloraniformethan, chloranil, chloranocryl, chlorantraniliprole,chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside,chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane,chlordecone, chlordimeform, chlordimeform hydrochloride,chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac,chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole,chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide,chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren,chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon,chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequatchloride, chlornidine, chlornitrofen, chlorobenzilate,chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron,chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin,chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron,chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim,chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos,chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal,chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos,chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II,cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide,cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop,clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium,clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone,clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl,clopyralid-olamine, clopyralid-potassium,clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet,cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel,clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA,codlelure, colophonate, copper acetate, copper acetoarsenite, copperarsenate, copper carbonate, basic, copper hydroxide, copper naphthenate,copper oleate, copper oxychloride, copper silicate, copper sulfate,copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl,coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol,crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure,cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide,cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide,cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin,cyclosulfamuron, cycloxydim, cycluron, cyenopyrafen, cyflufenamid,cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin,cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil,cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin,cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid,cyprosulfamide, cyromazine, cythioate, daimuron, dalapon,dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide,dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT,debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn,d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos,diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate,dicamba, dicamba-diglycolamine, dicamba-dimethylammonium,dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl,dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine,dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone,dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl,dichlormate, dichlormid, dichlorophen, dichlorprop,dichlorprop-2-ethylhexyl, dichlorprop-butotyl,dichlorprop-dimethylammonium, dichlorprop-ethylammonium,dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P,dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium,dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline,diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine,diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl,dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat,diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb,dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron,difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin,diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium,diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin,dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin,dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate,dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon,dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole,diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6,dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinosebacetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium,dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate,dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion,diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone,diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquatdibromide, disparlure, disul, disulfuram, disulfoton, disul-sodium,ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron,d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium,dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicinhydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure,doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone,edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothal, endothal-diammonium,endothal-dipotassium, endothal-disodium, endothion, endrin,enestroburin, EPN, epocholeone, epofenonane, epoxiconazole,eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan,esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole,etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron,ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron,ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol,ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen,ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethylformate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylenedibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercurybromide, ethylmercury chloride, ethylmercury phosphate, etinofen,etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos,eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos,fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole,fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos,fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan,fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl,fenoprop-butomethyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl,fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim,fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P,fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil,fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine,fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl,fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl,fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride,fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA,fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop,flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl,flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid,florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl,fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron,flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium,flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate,fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim,flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl,flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin,flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph,fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid,fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl,fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole,fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate,flupropanate-sodium, flupyradifurone, flupyrsulfuron,flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole,flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone,fluorochloridone, fluoroxypyr, fluoroxypyr-butomethyl,fluoroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole,flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil,flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen,fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde,formetanate, formetanate hydrochloride, formothion, formparanate,formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl,fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan,frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling,fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr,furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin,furfural, furilazole, furmecyclox, furophanate, furyloxyfen,gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins,gliftor, glufosinate, glufosinate-ammonium, glufosinate-P,glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime,glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium,glyphosate-isopropylammonium, glyphosate-monoammonium,glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium,glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatineacetates, halacrinate, halfenprox, halofenozide, halosafen,halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop,haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl,haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD,heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone,hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole,hexaflumuron, hexaflurate, hexylure, hexamide, hexazinone, hexylthiofos,hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo,hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide,hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil,imazalil nitrate, imazalil sulfate, imazamethabenz,imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic,imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin,imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr,imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos,imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate,iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan,indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane,iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium,iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate,ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone,iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol,IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos,isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin,isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane,isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron,isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl,isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos,japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid,jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan,jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenilehormone III, kadethrin, karbutilate, karetazan, karetazan-potassium,kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox,ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi,lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil,lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure,looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA,malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper,mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA,MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium,MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl,MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl,MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil,mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl,mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl,mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl,mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium,mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform,medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr,mefenpyr-diethyl, mefluidide, mefluidide-diolamine,mefluidide-potassium, megatomoic acid, menazon, mepanipyrim,meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride,mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride,mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron,mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone,metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop,metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron,metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron,methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole,methfuroxam, methidathion, methiobencarb, methiocarb,methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos,methometon, methomyl, methoprene, methoprotryne, methoquin-butyl,methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methylapholate, methyl bromide, methyl eugenol, methyl iodide, methylisothiocyanate, methylacetophos, methylchloroform, methyldymron,methylene chloride, methylmercury benzoate, methylmercury dicyandiamide,methylmercury pentachlorophenoxide, methylneodecanamide, metiram,metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb,metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone,metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos,mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox,mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron,monochloroacetic acid, monocrotophos, monolinuron, monosulfuron,monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquatdichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid,moxidectin, MSMA, muscalure, myclobutanil, myclozolin,N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled,naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyaceticacids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin,neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine,nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin,nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl,norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron,nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace,omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron,oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil,oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon,oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone,oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate,oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen,oxymatrine, oxytetracycline, oxytetracycline hydrochloride,paclobutrazol, paichongding, para-dichlorobenzene, parafluoron,paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion,parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid,penconazole, pencycuron, pendimethalin, penflufen, penfluoron,penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin,pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazineoxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl,phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea,phenylmercury acetate, phenylmercury chloride, phenylmercury derivativeof pyrocatechol, phenylmercury nitrate, phenylmercury salicylate,phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl,phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb,phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram,picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl,picloram-olamine, picloram-potassium, picloram-triethylammonium,picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin,pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide,piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide,piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl,pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim,polyoxorim-zinc, polythialan, potassium arsenite, potassium azide,potassium cyanate, potassium gibberellate, potassium naphthenate,potassium polysulfide, potassium thiocyanate, potassiumα-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, pretilachlor, primidophos, primisulfuron,primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese,proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol,profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl,prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb,prometon, prometryn, promurit, propachlor, propamidine, propamidinedihydrochloride, propamocarb, propamocarb hydrochloride, propanil,propaphos, propaquizafop, propargite, proparthrin, propazine,propetamphos, propham, propiconazole, propineb, propisochlor, propoxur,propoxycarbazone, propoxycarbazone-sodium, propyl isome,propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin,prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarbhydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute,proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid,pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl,pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole,pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl,pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II,pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb,pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl,pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon,pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl,pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole,pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan,pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia,quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl,quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine,quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop,quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl,quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide,rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin,rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong,salicylanilide, sanguinarine, santonin, schradan, scilliroside,sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz,semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin,siduron, siglure, silafluofen, silatrane, silica gel, silthiofam,simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor,sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodiumfluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodiumorthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide,sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram,spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine,streptomycin, streptomycin sesquisulfate, strychnine, sulcatol,sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone,sulfuram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron,sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid,sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep,tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium,TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide,tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron,tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin,tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim,terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane,tetrachlorvinphos, tetraconazole, tetradifon, tetrafluoron,tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul,thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole,thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluoron,thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron,thiencarbazone, thiencarbazone-methyl, thifensulfuron,thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime,thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclamoxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate,thiohempa, thiomersal, thiometon, thionazin, thiophanate,thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap,thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium,thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil,tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad,tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim,tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin,tretamine, triacontanol, triadimefon, triadimenol, triafamone,tri-allate, triamiphos, triapenthenol, triarathene, triarimol,triasulfuron, triazamate, triazbutil, triaziflam, triazophos,triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide,tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat,triclopyr, triclopyr-butotyl, triclopyr-ethyl,triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane,trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron,trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin,triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl,trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb,trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan,triptolide, tritac, triticonazole, tritosulfuron, trunc-call,uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin,valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate,vinclozolin, warfarin, warfarin-potassium, warfarin-sodium,xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols,xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin,zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram,zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone,α-multistriatin, and α-naphthaleneacetic acid.
 5. A compositionaccording to claim 1 further comprising an agriculturally acceptablecarrier.
 6. A composition according to claim 1 wherein said molecule isin the form of a pesticidally acceptable acid addition salt.
 7. Acomposition according to claim 1 wherein said molecule is in the form ofa salt derivative.
 8. A composition according to claim 1 wherein saidmolecule is in the form a hydrate.
 9. A composition according to claim 1wherein said molecule is a resolved stereoisomer.
 10. A compositionaccording to claim 1 wherein said molecule is in the form a crystalpolymorph.
 11. A composition according to claim 1 wherein said moleculehas a ²H in place of ¹H.
 12. A composition according to claim 1 whereinsaid molecule has a ¹⁴C in place of a ¹²C.
 13. A composition accordingto claim 1 further comprising a biopesticide.
 14. A compositionaccording to claim 1 further comprising one or more of the followingcompounds: (a)3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;(b)3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one;(c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; (d)4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; (e)3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethylethyl)phenyl]-1,2-benzenedicarboxamide;(f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; (g)2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; (h)2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; (i)2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; (j)2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; (k)2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; (l)2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; (m)3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide;(n)N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazone;(o)N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)hydrazonenicotine; (p)O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}S-methylthiocarbonate; (q)(E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine;(r)1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol;(s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate;and (t)N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.15. A composition according to claim 1 further comprising a compoundhaving one or more of the following modes of action:acetylcholinesterase inhibitor; sodium channel modulator; chitinbiosynthesis inhibitor; GABA and glutamate-gated chloride channelantagonist; GABA and glutamate-gated chloride channel agonist;acetylcholine receptor agonist; acetylcholine receptor antagonist; MET Iinhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholinereceptor; Midgut membrane disrupter; oxidative phosphorylationdisrupter, and ryanodine receptor (RyRs).
 16. A composition according toclaim 1 further comprising a seed.
 17. A composition according to claim1 further comprising a seed that has been genetically modified toexpress one or more specialized traits.
 18. A composition according toclaim 1 wherein said composition is encapsulated inside, or placed onthe surface of, a capsule.
 19. A composition according to claim 1wherein said composition is encapsulated inside, or placed on thesurface of, a capsule, wherein said capsule has a diameter of about100-900 nanometers or about 10-900 microns.